Intermediates for the preparation of (2-imidazolin-2-yl)thieno- and furo(2,3-b) and (3,2-b) pyridines

ABSTRACT

There is provided novel (2-imidazolin-2-yl)thieno and furo compounds, and intermediate compounds for the preparation thereof, and a method for controlling a wide variety of annual and perennial plant species therewith.

This is a continuation of abandoned application Ser. No. 176,542, filedApr. 1, 1988 which is a division of Ser. No. 929,681, filed Jan. 21,1987 (U.S. Pat. No. 4,752,323), which is a division of Ser. No. 676,133filed Nov. 29, 1984 (U.S. Pat. No. 4,650,514), which is acontinuation-in-part of abandoned Ser. No. 611,191, filed May 21, 1984,which is a continuation-in-part of abandoned U.S. Ser. No. 500,219,filed June 2, 1983.

The present invention relates to novel (2-imidazolin-2-yl)thieno- andfuropyridine compounds, and intermediates for the preparation of saidpyridine compounds and a method for controlling undesirable annual andperennial plant species therewith.

More particularly, this invention relates to6-(2-imidazolin-2-yl)thieno- and furo[2,3-b] and5-(2-imidazolin-2-yl)thieno- and furo[3,2-b]pyridine compounds and thecorresponding 2,3-dihydrothieno and 2,3-dihydrofuro compounds having thestructures (Ia) and (Ib): ##STR1## wherein represents a single or adouble bond; R₁ is C₁ -C₄ alkyl; R₂ is C₁ -C₄ alkyl or C₃ -C₆cycloalkyl; and when R₁ and R₂ are taken together with the carbon towhich they are attached they may represent C₃ -C₆ cycloalkyl optionallysubstituted with methyl; R₃ is hydrogen; C₁ -C₄ alkyl, which may beinterrupted by O or S and is optionally substituted with one of thefollowing groups: furyl, phenyl, halophenyl, C₁ -C₄ alkylphenyl, C₁ -C₄alkoxyphenyl or nitrophenyl; C₃ -C₆ alkenyl optionally substituted withone or two halogens; C₃ -C₆ alkynyl; or a cation of alkali metals,alkaline earth metals, manganese, copper, iron, ammonium or organicammonium; B is H, COR₄ or SO₂ R₅, provided that when B is COR₄, R₃cannot be hydrogen or a salt-forming cation; R₄ is C₁ -C.sub. 4 alkyl,chloromethyl or phenyl optionally substituted with one chloro, onenitro, one methyl, or one methoxy group; R₅ is C₁ -C₅ alkyl or phenyloptionally substituted with one methyl group, chloro or nitro; W is O orS; X is O, S, or, where is a single bond, X is S═O; Y and Y', Z and Z'are hydrogen, halogen, C₁ -C₆ alkyl, C₁ -C₆ alkoxy, C₁ -C₆ alkanoyloxy,C₁ -C₄ alkylthio, phenoxy, C₁ -C₄ haloalkyl, C₁ -C₄ haloalkoxy, nitro,cyano, C₁ -C₄ dialkylamino or phenyl optionally substituted with one ortwo C₁ -C₄ alkyl, C₁ -C₄ alkoxy, halogen, or any combination of two ofthese groups with the proviso that when Y and Z are the same group theyare H, halogen, alkyl or alkoxy, and when Y and Y' or Z and Z' are thesame group they are hydrogen or alkyl; and, when taken together, Y and Zmay form a ring in which YZ are represented by the structure --(CH₂)_(n)--, where n is an integer of 3 or 4, or ##STR2## where L, M, Q and R₇each represent hydrogen, halogen, C₁ -C₄ alkyl or C₁ -C₄ alkoxy, withthe proviso that only one of L, M, Q or R₇, may represent a substituentother than hydrogen, halogen, C₁ -C₄ alkyl or C₁ -C₄ alkoxy; thepyridine N-oxides thereof; and when R₁ and R₂ are not the same, theoptical isomers thereof; and, except when R₃ is a salt-forming cation,the acid addition salts thereof.

A preferred group of 6-(2-imidazolin-2-yl)thieno- andfuro[2,3-b]pyridine and 5-(2-imidazolin-2-yl)thieno- and furo[3,2-b]pyridine compounds have the formula shown as (Ia) and (Ib) above,wherein represents a single or a double bond; R₁ is C₁ -C₄ alkyl; R₂ isC₁ -C₄ alkyl or C₃ -C₆ cycloalkyl; and when R₁ and R₂ are taken togetherwith the carbon to which they are attached they may represent C₃ -C₆cycloalkyl optionally substituted with methyl; R₃ is hydrogen; C₁ -C₄alkyl, which may be optionally substituted with one of the followinggroups: furyl, phenyl, halophenyl, C₁ -C₄ alkylphenyl, C₁ -C₄alkoxyphenyl or nitrophenyl; C₃ -C₆ alkynyl; or a cation of alkalimetals, alkaline earth metals, ammonium or mono, di, tri or tetra C₁-C₂₂ alkylammonium; B is H, COR₄ or SO₂ R₅, provided that when B isCOR₄, R₃ cannot be hydrogen or a salt-forming cation; R₄ is C₁ -C₄alkyl, chloromethyl or phenyl optionally substituted with one chloro,one nitro, one methyl or one methoxy group; R₅ is C₁ -C₅ alkyl or phenyloptionally substituted with one methyl group, chloro or nitro; W is O orS; X is O, S, or, where is a single bond, S═O; Y and Y', Z and Z' arehydrogen, halogen, C₁ -C₆ alkyl, C₁ -C₆ alkoxy, C₁ -C₆ alkanoyloxy, C₁-C₄ haloalkyl, C₁ -C₄ haloalkoxy, nitro, C₁ -C₄ dialkylamino or phenylwith the proviso that when Y and Z are the same group they are H,halogen, alkyl or alkoxy, and that when is a single bond, Y, Y', Z andZ' are hydrogen, alkyl, alkoxy or halogen, and when Y and Y' or Z and Z'are the same group they are hydrogen or alkyl; and, when taken together,Y and Z may form a ring in which YZ are represented by the structure--(CH₂)_(n) --, where n is an integer selected from 3 or 4, or--CH═CH--CH═CH--; the pyridine N-oxides thereof; and when R₁ and R₂ arenot the same, the optical isomers thereof; and, except when R₃ is asalt-forming cation, the acid addition salts thereof.

A more preferred group of formula (Ia) and (Ib)6-(2-imidazolin-2-yl)thieno- and furo[2,3-b]pyridine and5-(2-imidazolin-2-yl)thieno- and furo[3,2-b]pyridine compounds are thosewherein represents a single bond; X is oxygen, sulfur, or S═O; Y and Zare hydrogen, methoxy, methyl, or chlorine, with the proviso that one ofY and Z is hydrogen; R₃ is hydrogen, furfuryl, propynyl, methyl or acation of alkali metals, alkaline earth metals, amonium or mono, di, trior tetra C₁ -C₂₂ alkylammonium; R₁ and R₂ are methyl, ethyl, isopropyl,or when taken together form a cyclohexyl or 2-methylcyclohexyl ring, andwhen R₁ and R₂ are not the same, the optical isomers thereof.

Another more preferred group of formula (Ia) and (Ib)6-(2-imidazolin-2-yl)thieno- and furo[2,3-b]pyridine and5-(2-imidazolin-2-yl)thieno- and furo [3,2-b]pyridine compounds arethose wherein X is oxygen or sulfur; B is H; Y and Z are hydrogen,methyl, ethyl, chlorine, bromine, methoxy or phenyl; R₃ is hydrogen,propynyl. furfuryl, methyl or a cation of alkali metals, alkaline earthmetals, ammonium or mono, di, tri or tetra C₁ -C₂₂ alkylammonium; R₁ andR₂ are methyl, ethyl, isopropyl, or when taken together form acyclohexyl or 2-methylcyclohexyl ring; W is O or S, and when R₁ and R₂are not the same, the optical isomers thereof.

A most preferred group of formula (Ia) 6-(2-imidazolin-2-yl)thieno- andfuro[2,3-b]pyridine compounds are those wherein X is oxygen or sulfur; Yis hydrogen or methyl; Z is hydrogen, chlorine or bromine, R₃ ishydrogen, propynyl, furfuryl or a sodium, ammonium or mono, di, tri ortetra C₁ -C₂₂ alkylammonium cation; W is O or S, and the optical isomersthereof.

It should also be understood that when B is H the imidazolinyl thieno-and furo[2,3-b] and [3,2-b]pyridines represented by formula (Ia) and(Ib) above may be tautomeric. While, for convenience, they are depictedby single structures identified as formula (Ia) and (Ib), they may existin either of the tautomeric forms illustrated as follows: ##STR3## Assuch, both tautomeric forms of said imidazolinylpyridines are meant tobe included under the formula (Ia) and (Ib) definition.

The present invention also relates to novel substituted thieno- andfuroimidazopyrrolopyridinedione compounds of structure (IIa) and (IIb)below and a method for controlling undesirable annual and perennialplant species therewith in soybeans and certain cereal crops: ##STR4##wherein X, Y, Y', Z, Z', W, R₁ and R₂ are as described for (Ia) and (Ib)above and wherein X, Y, Z, W, R₁ and R₂ in the preferred, more preferredand most preferred formula (IIa) and (IIb) compounds are as describedfor the preferred, more preferred and most preferred formula (Ia) andformula (Ib) compounds.

Herbicidal substituted pyridine and quinoline2-imidazolin-2-yl acids,esters and salts are disclosed in European Patent Application No.81103638.3 filed Dec. 1, 1981. The present invention relates to novelthieno- and furo[2,3-b]pyridines and thieno- and furo[3,2-b]pyridineswhich when substituted in the 6 or 5 position with an imidazolinone ringand in the 5 or 6 position with a group CO₂ R₃ as previously defined,provide potent herbicidal agents. The finding that imidazolinyl thieno-and -furopyridines provide potent herbicides is unexpected as there isno prior indication that such [2,3-b] or [3,2-b] ring systems may beemployed for any agronomic or herbicidal utility. This new class ofherbicidal agents is highly effective when applied as a pre- orpostemergence treatment, and individual members of this class exhibitunusual selectivity in soybean and cereal crops such as wheat, barley,rice, rye and oats. Further, it has been found that selectivity incereals may be enhanced when R₃ is H, by the preparation of esters,particularly furfuryl, alkynyl and haloalkenyl esters.

Additionally some members of this class exhibit unexpected plant growthregulating effects such as reduced plant height and antilodging activityand increased tillering in cereal crops.

The compounds of the present invention may conveniently be prepared fromthe appropriately substituted thieno- and furo[2,3-b] and[3,2-b]pyridinedicarboxylic acids and esters of formula (IIIa) and(IIIb): ##STR5## wherein X, Y and Z are as previously described and R ismethyl or ethyl.

Methods suitable for preparing novel formula (Ia) and formula (Ib)unsaturated compounds wherein is a double bond from the novel formula(IIIa) and (IIIb) pyridinedicarboxylic acid esters are illustrated inFlow Diagram I below.

Thus formula (IIIa) and (IIIb) diesters may be hydrolyzed to thecorresponding thieno- and furo-2,3-pyridinedicarboxylic acids of formula(IVa) and (IVb) by reaction thereof with a strong base such as potassiumhydroxide or sodium hydroxide. Acid anhydrides of formula (Va) and (Vb)may then be prepared by treatment of the formula (IVa) and (IVb)pyridinedicarboxylic acids with, for example, acetic anhydride. Reactionof formula (Va) and (Vb) anhydrides with an appropriately substitutedaminocarboxamide or aminothiocarboxamide depicted by formula (VI) yieldscarbamoyl nicotinic acids of formula (VIIa) and (VIIb). Treatment of thethus-formed formula (VIIa) and (VIIb) carbamoyl nicotinic acids withabout 2 to 10 molar equivalents of aqueous or aqueous alcoholic sodiumor potassium hydroxide, preferbly under a blanket of inert gas such asnitrogen, cooling and acidifying to pH 2 to 4 with a strong mineral acidsuch as hydrochloric acid or sulfuric acid gives herbicidally effective6-(4,4-disubstituted-5-oxo-(or thioxo)-2-imidazolin-2-yl)thieno- andfuro[2,3-b]pyridine-5-carboxylic acids, and5-(4,4-disubstituted-5-oxo-(or thioxo)-2-imidazolin-2-yl)thieno- andfuro[3,2-b]pyridine-6-carboxylic acids encompassed by formulas (Ia) and(Ib).

Formula (Ia) and (Ib) 5 or 6-(2-imidazolin-2-yl)thieno- and furopyridineesters, wherein RHD 3 represents a substituent other than hydroge or asalt-forming cation, and R₁, R₂, X, Y and Z are as described above canbe prepared by reacting a novel thieno- orfuroimidazopyrrolopyridinedione, represented by formulas (IIa) and(IIb), hereinbelow, in Flow Diagram (II), with an appropriate alcoholand corresponding alkali metal alkoxide at a temperature ranging betweenabout 20° C. and about 50° C.

Formula (IIa) and (IIb9 novel thieno- andfuroimidazopyrrolopyridinediones may conveniently be prepared fromformula (Ia) and (Ib) acids, where B is H by treatment with oneequivalent of dicyclohexylcarbodiimide in an inert solvent such asmethylene chloride as illustrated in Flow Diagram (II) below. ##STR6##where M₁ is an alkali metal, and X, Y, Z, R₁, R₂ and R₃ are as abovedefined.

Many formula (IIIa) thieno[2,3-b]pyridinedicarboxylic acids and (IIIb)thieno[3,2:b]pyridinedicarboxylic acids may conveniently be prepared byreacting the appropriately substituted 2 or 3-aminothiophene of formula(VIIIa) or (VIIIb), where R is hydrogen or chloro, with a C₁ -C₄ alkylester of acetylenedicarboxylic acid of formula (IX) as described byBleckert et al. Chem. Ber. 1978, 106, 368. The thus-formedβ-aminothieno-α,β-unsaturated ester of formula (X) is then reacted withan immonium salt depicted by the formula Cl--CH═N.sup.⊕ --(R'")₂Cl.sup.⊖ wherein R'" is C₁ 14 C₆ alkyl or ##STR7## wherein n' is 4 or 5,in the presence of a low boiling chlorinated hydrocarbon solvent such asmethylene chloride or dichloroethane at a temperature between about 40°C. and 90° C., for a period of time sufficient to essentially completethe reaction and yield the formula (IIIa) [2,3-b]thieno- or (IIIb)[3,2-b]thieno-2,3-pyridinedicarboxylic acid as the dialkyl ester asillustrated in Flow Diagram (III) below.

Formula (IIIb) furo[3,2-b]pyridinedicarboxylic acids may be prepared byreacting 3-amino-2-formylfuran of formula (XI) prepared by the method ofS. Gronowitz et al., Acta Chemica Scand B29 224(1975) with ethyloxalacetate to give formula (IIIb) furopyridine compounds directly, asillustrated in Flow Diagram (IV) below while formula (IIIa)furo[2,3-b]pyridine compounds where Y and Z are H are obtained bybromination of the reaction product (XII) of acetoacetamide with thediethyl ester of ethoxymethyleneoxalacetic acid followed by treatmentwith sodium borohydride and para-toluene sulfonic acid in refluxingxylene as illustrated in Flow Diagram (V) below.

Formula (IIIb) 2,3-dihydrofuro[3,2-b] and thieno[3,2-b]pyridine may beprepared by the reaction of diethylethoxymethylene oxalacetate with amixture of enamines derived from 3-keto-tetrahydrofuran or3-ketotetrahydrothiophene, followed by treatment with ammonia orammonium, as illustrated in Flow Diagram (VI).

This procedure is described in abandoned application for U.S. LettersPatent, Ser. No. 612,531 of J. Johnson, filed May 21, 1984. ##STR8##wherein R₁ and R₂ each represents C₁ -C₆ alkyl or taken together withthe nitrogen atom to which they are attached form a 5 or 6 memberedsaturated heterocyclic ring, optionally containing at most 2 heteroatoms.

Formula (IIIa) furo[2,3-b]pyridine compounds where Z is H and Y is alkylor optionally substituted phenyl are prepared by reaction of anacetylene compound with the iodopyridine diester (VII) [preparation ofthis compound VII is described in J. Prakt. Chem., 148; 72(1937)], inthe presence of cuprous salts, an amine base, and a palladium (II)catalyst as shown in Flow Diagram (VII). ##STR9##

Substituents represented by Y and Z in formula (Ia), (Ib), (IIa)and(IIb) compounds of the present invention may be prepared either byusing the appropriately substituted starting material for thepreparation of formula (IIIa) and (IIIb) thieno- andfuropyridine-5,6-dicarboxylic acid esters or by electrophilicsubstitution (halogenation, nitration, sulfonation, etc.) directly uponFormula (IIIa) or (IIIb) diesters or Formula (Ia) or (Ib) finalproducts, wherein at least one of Y or Z is hydrogen. These substitutedFormula (IIIa), (IIIb), (Ia) and (Ib) compounds then may be used asstarting materials for additional Y and Z substitution by displacement,reduction, oxidation, etc. Representative substituted (IIIa) and (IIIb)compounds which may be prepared by these procedures are as illustratedbelow.

    ______________________________________                                         ##STR10##                                                                     ##STR11##                                                                    X         Y         Z             R                                           ______________________________________                                        S         H         H             CH.sub.3                                    S         H         Br            CH.sub.3                                    S         CH.sub.3  H             CH.sub.3                                    S         H         Cl            CH.sub.3                                    S         Cl        Cl            CH.sub.3                                    S         H         I             CH.sub.3                                    S         H         NO.sub.2      CH.sub.3                                    S         Br        Br            CH.sub.3                                    S         CH.sub.3  Cl            CH.sub.3                                    S         H         CH.sub.3      CH.sub.3                                    S         Cl        H             CH.sub.3                                    S         CH.sub.3  CH.sub.3      CH.sub.3                                    S         H         CN            CH.sub.3                                    S         H         OCH.sub.3     CH.sub.3                                    S         H         N(CH.sub.3).sub.2                                                                           CH.sub.3                                    S         H         SCH.sub.3     CH.sub.3                                    S         H         OCF.sub.2 H   CH.sub.3                                    O         H         H             C.sub.2 H.sub.5                             O         H         Br            CH.sub. 3                                   O         H         Br            C.sub.2 H.sub.5                             O         H         Cl            CH.sub.3                                    O         H         Cl            C.sub.2 H.sub.5                             O         CH.sub.3  H             CH.sub.3                                    O         CH.sub.3  H             C.sub.2 H.sub.5                             O         H         CH.sub.3      CH.sub.3                                    O         C.sub.2 H.sub.5                                                                         H             CH.sub.3                                    O         H         C.sub.2 H.sub.5                                                                             CH.sub.3                                    O         CH.sub.3  CH.sub.3      CH.sub.3                                    S         (CH.sub.2).sub.3        CH.sub.3                                    S         (CH.sub.2).sub.4        CH.sub.3                                    S         (CH).sub.4              CH.sub.3                                    S         C.sub.6 H.sub.5                                                                         H             CH.sub.3                                    O         C.sub.6 H.sub.5                                                                         H             CH.sub.3                                    S         H                                                                                        ##STR12##    CH.sub.3                                    S         H         OC.sub.6 H.sub.5                                                                            CH.sub.3                                    O         H         OC.sub.6 H.sub.5                                                                            CH.sub.3                                    O         CF.sub.3  H             CH.sub.3                                    O         H         NO.sub.2      C.sub.2 H.sub.5                             O         Br        Br            C.sub.2 H.sub.5                             O         H         C.sub.6 H.sub.5 S                                                                           C.sub.2 H.sub.5                             O         H         CF.sub.3      C.sub.2 H.sub.5                             ______________________________________                                    

Additionally, novel herbicidal 2,3-dihydrothieno[2,3-b] and[3,2-b]pyridine compounds may be obtained by starting the sequence inFlow Diagram (III) above with a dihydrothiophenimin hydrochloride. Novelherbicidal 2,3-dihydro furo[2,3-b] and [3,2-b]pyridines may be preparedby catalytic reduction of the formula (Ia) or (Ib) (2-imidazolin-2-yl)product, or (IIIa) and (IIIb) furo[2,3-b] and[3,2-b]pyridine-5,6-diesters as for example with hydrogen and palladiumon carbon, provided that Y and Z are substituents which are not reducedby such a procedure. Other 2,3-dihydrofuro[2,3-b]pyridines are preparedby the reduction-rearrangement of a bromo ketone with sodium borohydridefollowed by treatment with triethylamine, and p-toluenesulfonic acid asshown in Flow Diagram (VIII). This then provides novel 2,3-dihydroherbicidal compounds illustrated below. ##STR13## wherein X, Y, Y', Z,Z', W, B, R₁ and R₃ are as described for (Ia) and (Ib). ##STR14##

The formula (Ia) and formula (Ib) 6-(2-imidazolin-2-yl)thieno- andfuro[2,3-b]pyridines and 5-(2-imidazolin-2-yl)thieno- andfuro[3,2-b]pyridines and the formula (IIa) and formula (IIb)imidazopyrrolopyridinediones of the present invention are exceedinglyeffective herbicidal agents useful for the control of an exceptionallywide variety of herbaceous and woody annual and perennialmonocotyledonous and dicotyledonous plants. Moreover, these compoundsare herbicidally effective for controlling weeds indigenous to both dryland and wet land areas. They are also useful as aquatic herbicides andare unique in their effectiveness in controlling the above-said plantswhen applied to the foilage thereof or to soil or water containing seedsor other propagating organs of said plants such as tubers, rhizomes orstolons, at rates of from about 0.016 to 4.0 kg/ha, and preferably atrates from about 0.032 to 2.0 kg/ha.

It is, of course, obvious that rates of application above the 4.0 kg/halevel can also be used to effectively kill undesirable plant species;however, rates of application of toxicant above the level necessary tokill the undesirable plants should be avoided since application ofexcessive amounts of toxicant is costly and serves no useful function inthe environment.

Among the plants which may be controlled with the compounds of thisinvention are: Elatine triandra, Sagittaria pygmaea, Scirpus hotarui,Cyperus serotinus, Eclipta alba, Cyperus difformis, Rotala indica,Lindernia pyridoria, Echinochloa crus-galli, Digitaria sanguinalis,Setaria viridis, Cyperus rotundus, Convolvulus arvensis, Agropyronrepens, Datura stramonium, Alopercurus myosuroides, Ipomoea spp., Sidaspinosa, Ambrosia artemisiifolia, Eichhornia crassipes, Xanthiumpensylvanicum, Sesbania exaltata, Avena fatua, Abutilon theophrasti,Bromus tectorum, Sorghum halepense, Lolium spp., Panicumdichotomiflorum, Matricaria spp., Amaranthus retroflexus, Cirsiumarvense and Rumex iaponicus.

It has been found that the formula (Ia) and (Ib)(2-imidazolin-2-yl)thieno- and furopyridines are generally selectiveherbicides, particularly effective for controlling undesirable weeds inthe presence of leguminous crops such as soybeans, and cereal crops suchas wheat, barley, oats and rye. However, certain of the formula (Ia) andformula (Ib) compounds are less selective than others in this series.

It has also been found that several of the formula (Ia) and formula (Ib)(2-imidazolin-2-yl)pyridines are effective as antilodging agents incereal crops when applied at rates of application between about 0.016 to4.0 kg hectare. At rates of application not exceeding about 0.010 kg perhectare, it has also been found that certain of the formula (Ia) andformula (Ib) thieno- and furopyridines are effective for increasingbranching of leguminous crops and tillering of cereal crops.

Since the formula (Ia) and formula (Ib) imidazolinylthieno- andfuropyridines and derivatives, wherein R₃ is a salt-forming cation, arewater soluble, these compounds can simply be dispersed in water andapplied as a dilute aqueous spray to the foliage of plants or to soilcontaining propagating organs thereof. These salts also lend themselvesto formulation as flowable concentrates.

The formula (Ia) and formula (Ib) (2-imidazolin-2-yl)thieno- andfuropyridines and the formula (IIa) and formula (IIb)imidazopyrrolopyridinediones can also be formulated as wettable powders,flow concentrates, emulsifiable concentrates, granular formulations andthe like.

Wettable powders can be prepared by grinding together about 20% to 45%by weight of a finely divided carrier such as kaolin, bentonite,diatomaceous earth, attapulgite, or the like, 45% to 80% by weight ofthe active compound, 2% to 5% by weight of a dispersing agent such assodium lignosulfonate, and 2% to 5% by weight of a nonionic surfactant,such as octylphenoxy polyethoxy ethanol, nonylphenoxy polyethoxy ethanolor the like.

A typical flowable liquid can be prepared by admixing about 40% byweight of the active ingredient with about 2% by weight of a gellingagent such as bentonite, 3% by weight of a dispersing agent such assodium lignosulfonate, 1% by weight of polyethylene glycol and 54% byweight of water.

A typical emulsifiable concentrate can be prepared by dissolving about5% to 25% by weight of the active ingredient in about 65% to 90% byweight of N-methylpyrrolidone, isophorone, butyl cellosolve,methylacetate or the like and dispersing therein about 5% to 10% byweight of a nonionic surfactant such as an alkylphenoxy polyethoxyalcohol. This concentrate is dispersed in water for application as aliquid spray.

When the compounds of the invention are to be used as herbicides wheresoil treatments are involved, the compounds may be prepared and appliedas granular products. Preparation of the granular product can beachieved by dissolving the active compound in a solvent such asmethylene chloride, N-methylpyrrolidone or the like and spraying thethus prepared solution on a granular carried such as corncob grits,sand, attapulgite, kaolin or the like.

The granular product thus prepared generally comprises about 3% to 20%by weight of the active ingredient and about 97% to 80% by weight of thegranular carrier.

In order to facilitate a further understanding of the invention, thefollowing examples are presented primarily for the purpose ofillustrating certain more specific details thereof. The invention is notto be deemed limited thereby except as defined in the claims. Unlessotherwise noted, all parts are by weight.

EXAMPLE 1 Preparation of dimethylthieno[3,2-b]pyridine-5,6-dicarboxylate ##STR15##

A mixture of isopropyl-3-thiophenecarbamate (177 g; 0.975 mol) inmethanol (1.2 l) and water (2.8 l) containing sodium hydroxide (200 g)is heated at reflux for four hours. Methanol is removed under reducedpressure and the cooled reaction extracted with ether (5 l), and theseextracts are washed with water, aqueous sodium chloride and dried.Evaporation under reduced pressure affords 3-aminothiophene as an oil in57% crude yield.

3-Aminothiophene is redissolved in methanol (500 mL) cooled in an icebath and dimethylacetylenedicarboxylate (80 g; 0.50 mol) is addeddropwise. The mixture is stirred at room temperature for 15 hours and 30minutes, the methanol removed under reduced pressure and1,2-dichloroethane is added. This solvent is also evaporated off to givedimethyl 3-thienylaminobutenedioate as an oil.

A Vilsmeier reagent is prepared by adding dropwise, with stirringphosphorus oxychloride (86 g, 0.56 mol) to a cooled (5° C.) solution ofDMF (41 g, 0.56 mol) in 1,2-dichloroethane (200 mL). This reagent isstirred at room temperature for one hour and 40 minutes, diluted with1,2-dichloroethane (100 mL), cooled to 5° C. and then the above dimethylester dissolved in 1,2-dichloroethane (400 mL) is added to the Vilsmeierreagent at 5° C. dropwise over a 25 minute period. The reactiontemperature is raised to room temperature for 15 minutes, then to refluxfor a further two hours and 25 minutes. The cooled reaction mixture ischromatographed directly on a silica gel column affording 35.7 g (15%)of dimethyl thieno[3,2-b]pyridine-5,6-dicarboxylate mp 124°-125.5° C.after crystallization from hexane-ethylacetate. A second crop 10.3 gwith mp 121°-124° C. is obtained giving an overall yield from isopropyl3-thiophenecarbamate of 19%.

Utilizing the above procedure and substituting the appropriatesubstituted aminothiophene for isopropyl 3-aminothiophenecarbamateyields the compounds illustrated below.

    ______________________________________                                         ##STR16##                                                                    Y       Z             R      mp °C.                                    ______________________________________                                        H       H             CH.sub.3                                                                             126-127                                          CH.sub.3                                                                              H             CH.sub.3                                                                             --                                               Cl      H             CH.sub.3                                                                             149-151                                          ______________________________________                                    

EXAMPLE 2 Preparation of dimethylthieno[3,2-b]pyridine-5,6-dicarboxylate ##STR17##

To concentrated sulfuric acid (170 mL), stirred at room temperature isadded in portions 3-acetylamino-2-formylthiophene (17.5 g, 0.103 mol).The mixture is heated at 50° C. for 30 minutes, cooled and poured intoan ice-water mixture. After neutralizing with an excess of sodiumacetate, the mixture is ether (1×2 mL) extracted. The organic layer wasdried over anhydrous Na₂ SO₄ and stripped to a dark red gum consistingof 3-amino-2-formylthiophene. Dimethylacetylenedicarboxylate (DMAD) (13mL) in acetic acid (5 mL), piperidine (5 mL), methylene chloride (100mL) and toluene (100 mL) is added to the 3-amino-2-formylthiophene andthe mixture stirred overnight. Methylene chloride is removed bydistillation and then the mixture heated at reflux for 24 hours. Aftercooling an additional 13 mL of DMAD is added and the reaction heated toreflux again for seven and one-half hours. After standing for 60 hoursat room temperature, the solvents are removed and the dimethylthieno[3,2-b]pyridine-5,6-dicarboxylate product is obtained bychromatography, after eluting with hexane-ethyl acetate, mp 124°-125° C.

EXAMPLE 3 Preparation of dimethyl3-chloro[3,2-b]pyridine-5,6-dicarboxylate and dimethyl2,3-dichlorothieno[3,2-b]pyridine-5,6-dicarboxylate ##STR18##

A solution of dimethyl thieno[3,2-b]pyridine-5,6-dicarboxylate (15 g0.0525 mol) in acetic acid (680 mL) and sodium acetate (86 g, 0.093 mol)is maintained at 58° C. while chlorine is slowly introduced during fivehours and 45 minutes. After reaction is complete, the mixture is flushedwith nitrogen, ethyl acetate (200 mL) is added and solid sodium chloridefiltered off and washed with ethyl acetate. The mother liquors andwashes are combined and the solvents removed under reduced pressure. Theresidue is dissolved in methylene chloride and the solution washed withwater, back extracted with methylene chloride and the combined methylenechloride layers washed with aqueous sodium bicarbonate, dried andstripped to give 18 g of solid. Chromatography on silica gel with 15%ethyl acetatehexane, then 20% ethyl acetate-hexane gives the2,3-dichloro compound, mp 173°-178° C., 1.3 g, followed by the3-chlorothieno compound mp 166°-173° C. after crystallization from ethylacetate-hexane.

EXAMPLE 4 Preparation of dimethyl3-bromothieno[3,2-b]pyridine-5,6-dicarboxylate ##STR19##

A solution of bromine (20 g, 0.125 mol) in acetic acid (50 mL) is addeddropwise over three hours to a solution of dimethylthieno[3,2-b]pyridine-5,6-dicarboxylate, (26.3 g, 0.104 mol), containingsodium acetate (17.2 g, 0.2 mol) in acetic acid (300 mL) at 85° C.Additional sodium acetate (18 g) and bromine (20 g) in acetic acid (50mL) is added over an hour and the mixture stirred at 85° C. overnight.Bromine (10 g) is added in one portion then left at 85° C. for fourhours. The mixture is cooled and treated with aqueous sodium bisulfite,diluted with ethyl acetate and concentrated. The reaction product ispartitioned between water and methylene chloride and the organic layerwashed with aqueous sodium chloride and the solvent removed. The residueis washed with ether to give 25 g of crude product, mp 165°-168° C.Recrystallization from methanol gave needles of dimethyl 3-bromothieno[3,2-b]pyridine-5,6-dicarboxylate, mp 168°-169° C.

EXAMPLE 5 Preparation of thieno[3,2-b]pyridine-5,6-dicarboxylic acid##STR20##

Dimethyl thieno[3,2-b]pyridine-5,6-dicarboxylate (3.75 g, 0.0149 mol) isadded to a solution of sodium hydroxide (1.8 g, 0.045 mol) in water (20mL) and the mixture is warmed at 60° C. for 20 hours. The reactionmixture is diluted with water, cooled in an ice bath, and acidified bythe addition of concentrated hydrochloric acid. A precipitate ofthieno[3,2-b]pyridine-5,6-dicarboxylic acid is filtered off and driedovernight to give 3.1 g (93%) mp>380° C.

Utilizing the above procedure and substituting the appropriatesubstituted thieno[3,2-b]pyridine-5,6-dicarboxylic acid diester yieldsthe compounds illustrated below.

    ______________________________________                                         ##STR21##                                                                    Y            Z          mp °C.                                         ______________________________________                                        H            H          >380                                                  H            Cl         None taken                                            H            Br         >380                                                  H            I          --                                                    H            F          --                                                    H            CN         --                                                    H            OCH.sub.3  --                                                    H            NO.sub.2   --                                                    H            N(CH.sub.3).sub.2                                                                        --                                                    CH.sub.3     H          --                                                    H            CH.sub.3   --                                                    CH.sub.3     CH.sub.3   --                                                    H            OCHF.sub.2 --                                                    H            SCH.sub.3  --                                                    H            SO.sub.2 N(CH.sub.3).sub.2                                                               --                                                    C.sub.6 H.sub.5                                                                            H          --                                                    (CH.sub.2).sub.3    --                                                        (CH.sub.2).sub.4    --                                                        (CH).sub.4          --                                                        Cl           Cl         --                                                    H            C.sub.6 H.sub.5                                                                          --                                                    C.sub.6 H.sub.5                                                                            H          --                                                    H            OC.sub.6 H.sub.5                                                                         --                                                    CF.sub.3     H          --                                                    C.sub.2 H.sub.5                                                                            H          --                                                    H            C.sub. 2 H.sub.5                                                                         --                                                    H            SC.sub.6 H.sub.5                                                                         --                                                    H            CF.sub.3   --                                                    H            CHO        --                                                    H            CH.sub.2 Cl                                                                              --                                                    ______________________________________                                    

EXAMPLE 6 Preparation of 3-chlorothieno[3,2-b]pyridine 5,6-dicarboxylicacid anhydride ##STR22##

3-Chlorothieno[3,2-b]pyridine-5,6-dicarboxylic acid (1.45 g) is heatedat 85° to 90° C. for 30 minutes then 90° to 102° C. for 30 minutes inacetic anhydride (7 mL). The reaction is cooled, the solids filtered offand washed with ether to give 1.2 g of3-chlorothieno[3,2-b]pyridine-5,6-dicarboxylic acid anhydride. Theproton magnetic resonance spectrum is consistant with the structure.

Utilizing the above procedure and substituting the appropriatepyridine-5,6-dicarboxylic acid for3-chlorothieno[3,2-b]pyridine-5,6-dicarboxylic acid yields the compoundsillustrated below.

    ______________________________________                                         ##STR23##                                                                    Y           Z          mp °C.                                          ______________________________________                                        H           H          266-267                                                H           Cl         Solid no mp                                                                   obtained                                               H           Br         >380                                                   Cl          H          --                                                     Cl          Cl         --                                                     H           NO.sub.2   --                                                     CH.sub.3    H          --                                                     H           N(CH.sub.3).sub.2                                                                        --                                                     H           SCH.sub.3  --                                                     H           OCH.sub.3  --                                                     H           CH.sub.3   --                                                     H           F          --                                                     H           I          --                                                     CH.sub.3    CH.sub.3   --                                                     H           CN         --                                                     H           OCHF.sub.2 --                                                     H           SO.sub.2 N(CH.sub.3).sub.2                                                               --                                                     (CH.sub.2).sub.3   --                                                         (CH.sub.2).sub.4   --                                                         (CH).sub.4         --                                                         H           C.sub.6 H.sub.5                                                                          --                                                     C.sub.6 H.sub.5                                                                           H          --                                                     H           OC.sub.6 H.sub.5                                                                         --                                                     CF.sub.3    H          --                                                     C.sub.2 H.sub. 5                                                                          H          --                                                     H           C.sub.2 H.sub.5                                                                          --                                                     H           SC.sub.6 H.sub.5                                                                         --                                                     H           CF.sub.3   --                                                     H           CHO        --                                                     H           CH.sub.2 Cl                                                                              --                                                     ______________________________________                                    

EXAMPLE 7 Preparation of5-[(1-carbamoyl-1,2-dimethylpropyl)-3-chlorothieno[3,2-b]pyridine-6-carboxylicacid ##STR24##

2-Amino-2,3-dimethylbutyramide (0.71 g) all in one portion is added to astirred solution of 3-chlorothieno[3,2-b]pyridine-5,6-dicarboxylic acidanhydride, (1.2 g) in THF (1.0 mL). After standing for five minutes, theice bath is removed and the reaction stirred at room temperature for 28hours. THF (5 mL) is added and the mixture heated at reflux for twohours and then set aside overnight. The cooled mixture is filtered andthe collected solid washed with ether to give 1.4 g of the desired5-[(1-carbamoyl-1,2-dimethylpropyl)carbamoyl]-3-chlorothieno[3,2-b]pyridine-6-carboxylicacid.

Utilizing the above procedure and substituting the appropriatepyridine-5,6-dicarboxylic acid anhydride for3-chlorothieno[3,2-b]pyridine-5,6-dicarboxylic acid anhydride and theappropriate aminoamide yields the compounds illustrated below.

    ______________________________________                                         ##STR25##                                                                    Y       Z           R.sub.1 R.sub.2                                                                             mp °C.                               ______________________________________                                        H       H           CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       Cl          CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            not pure                                    Cl      H           CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          Cl      Cl          CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       Br          CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       CH.sub.3    CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       NO.sub.2    CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       N(CH.sub.3).sub.2                                                                         CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       SCH.sub.3   CH.sub.3                                                                               .sub. -i-C.sub.3 H.sub.7                                                           --                                          H       OCH.sub.3   CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          CH.sub.3                                                                              H           CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       H           CH.sub.3                                                                              C.sub.3 H.sub.7                                                                     --                                          H       H           CH.sub.3                                                                              C.sub.2 H.sub.5                                                                     --                                          H       OCHF.sub.2  CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          CH.sub.3                                                                              CH.sub.3    CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       CN          CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       F           CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       I           CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       SO.sub.2 N(CH.sub.3).sub.2                                                                CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          C.sub.6 H.sub.5                                                                       H           CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          (CH.sub.2).sub.3                                                                              CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                              --                                            (CH.sub.2).sub.4                                                                              CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                              --                                            (CH).sub.4      CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                              --                                            H       C.sub.6 H.sub.5                                                                           CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          C.sub.2 H.sub.5                                                                       H           CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       OC.sub.6 H.sub.5                                                                          CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       CH.sub.2 Cl CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          CF.sub.3                                                                              H           CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       C.sub.2 H.sub.5                                                                           CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       CHO         CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       CF.sub.3    CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          H       SC.sub.6 H.sub.5                                                                          CH.sub.3                                                                               .sub.-i-C.sub.3 H.sub.7                                                            --                                          ______________________________________                                    

EXAMPLE 8 Preparation of5-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)thieno[3,2-b]pyridine-6-carboxylicacid ##STR26##

Thieno[3,2-b]pyridine-5,6-dicarboxylic acid (2.5 g, 0.011 mol) is heatedslowly to 85° C. for one hour with acetic anhydride (25 mL), thencooled, filtered and washed with diethyl ether to give the anhydride asa solid, mp 266°-267° C. A mixture of the anhydride and2-amino-2,3-dimethylbutyramide (2.6 g, 0.02 mol) in THF (70 mL) isstirred at room temperature for 15 hours.

After heating at reflux for two hours, the mixture is cooled and dilutedwith THF (50 mL). Solid5-[(1-carbamoyl-1,2-dimethylpropyl)carbamoyl]thieno[3,2-b]-pyridine-6-carboxylicacid is filtered off, washed with ether and dried. The above solid ismixed with an aqueous 60 mL) solution of sodium hydroxide (6 g 0.05 mol)and heated at 85° C. for two hours and 30 minutes, then set aside atroom temperature overnight. After cooling in an ice bath, the mixture isacidified to pH 3 with concentrated hydrochloric acid. A solid (3 g) isfiltered off and dried. Crystallization from ethyl acetate affords(5-(5-isopropyl-5-methyl-4-oxo-2-imidazoling-2-yl)thieno[3,2-b]pyridine-6-carboxylicacid, mp 242°-244° C. in 46% yield.

Utilizing the above procedure and substituting the appropriatepyridine-5,6-dicarboxylic acid forthieno[3,2-b]pyridine-5,6-dicarboxylic acid yields the compoundsillustrated below.

    ______________________________________                                         ##STR27##                                                                    Y            Z          mp °C.                                         ______________________________________                                        H            H          242-244                                               H            Cl         238-239                                               H            Br         226-227                                               Cl           H          247-248                                               Cl           Cl         --                                                    H            CH.sub.3   --                                                    CH.sub.3     H          --                                                    H            NO.sub.2   --                                                    H            N(CH.sub.3).sub.2                                                                        --                                                    H            SC.sub.6 H.sub.5                                                                         --                                                    H            SCH.sub.3  --                                                    H            OCH.sub.3  --                                                    H            OCHF.sub.2 --                                                    CH.sub.3     CH.sub.3   --                                                    H            CH         --                                                    H            SO.sub.2 N(CH.sub.3).sub.2                                                               --                                                    C.sub.6 H.sub.5                                                                            H          --                                                    (CH.sub.2).sub.3    --                                                        (CH.sub.2).sub.4    --                                                        (CH.sub.2).sub.4    --                                                        H            C.sub.6 H.sub.5                                                                          --                                                    H            OC.sub.6 H.sub.5                                                                         --                                                    CF.sub.3     H          --                                                    C.sub.2 H.sub.5                                                                            H          --                                                    H            C.sub.2 H.sub.5                                                                          --                                                    H            I          --                                                    H            F          --                                                    H            CHO        --                                                    H            CH.sub.2 Cl                                                                              --                                                    H            CF.sub.3   --                                                    ______________________________________                                    

EXAMPLE 9 Preparation of diethyl furo[3,2-b]pyridine-5,6-dicarboxylate##STR28##

3-Amino-2-formylfuran, prepared from 3-azido-2-formylfuran (8.9 g 0.065mol) is dissolved in ethanol and to this solution diethyl oxalacetate(12.23 g, 0.065 mol) and ten drops of piperidine are added. In additionpulverized 3A° molecular sieve is added and the reaction stirred at65°-60° C. for three hours, then additional diethyl oxalacetate (2.2 g)is added. The reaction is essentially complete after 12 hours at 55°-60°C. On cooling the reaction is filtered, and the filtrate concentratedand then dissolved in ethyl acetate, water washed, then brine washed,dried over anhydrous magnesium sulfate and stripped to dryness. Theresidue is dissolved in 3:1 hexane:ethyl acetate and passed through aflash chromatographic column in two stages. First it is filtered byvacuum through a four to five inch pad of silica from which the lastthree fractions containing the required product are collected andcombined. These combined fractions are then passed through a six inchcolumn eluting under pressure with ethyl acetate:hexane 3:1 and 2.1.Diethyl furo[3,2-b]-pyridine-5,6-dicarboxylate 4.15 g (24%) is obtainedafter crystallization from hexane-ether, of mp 60°64° C., and with a masspectrum m/e of 264.

Utilizing the above procedure and substituting the appropriate furan for3-amino-2-formylfuran yields the compound illustrated below.

    ______________________________________                                         ##STR29##                                                                    Y           Z          R      mp °C.                                   ______________________________________                                        H           H          C.sub.2 H.sub.5                                                                      60-64                                           H           Cl         C.sub.2 H.sub.5                                                                      --                                              CH.sub.3    H          C.sub.2 H.sub.5                                                                      --                                              H           CH.sub.3   C.sub.2 H.sub.5                                                                      --                                              C.sub.2 H.sub.5                                                                           H          C.sub.2 H.sub.5                                                                      --                                              H           C.sub.2 H.sub.5                                                                          C.sub.2 H.sub.5                                                                      --                                              CH.sub.3    CH.sub.3   C.sub.2 H.sub.5                                                                      --                                              ______________________________________                                    

EXAMPLE 10 Preparation of furo[3,2-b]pyridine-5,6-dicarboxylic acid##STR30##

Furo[3,2-b]pyridine-5,6-dicarboxylic acid, diethyl ester (1.1 g, 0.0042mol) is dissolved in 95% ethanol (20 mL) containing 10% aqueous sodiumhydroxide (20 mL) and set aside at 0° C. for two days. The mixture iscooled, acidified and the solvent removed under reduced pressure. Water5 mL is added and the hydrated product diacid obtained as a brown solidby filtration, 3.31 g (99%), mp 183° C. (dec). Anal calcd. as C₉ H₅NO₅.21/2H₂ O C, 42.86; H, 3.99; N, 5.55 found: C, 42.63; H, 2.63; N,5.46.

Utilizing the above procedure and substituting the appropriatefuro[3,2-b]pyridine-5,6-dicarboxylic ester yields the compoundsillustrated below.

    ______________________________________                                        Y           Z         R      mp ° C.                                   ______________________________________                                        H           H         H      183 (dec)                                        H           Cl        C.sub.2 H.sub.5                                                                      --                                               CH.sub.3    H         C.sub.2 H.sub.5                                                                      --                                               H           CH.sub.3  C.sub.2 H.sub.5                                                                      --                                               C.sub.2 H.sub.5                                                                           H         C.sub.2 H.sub.5                                                                      --                                               H           C.sub.2 H.sub.5                                                                         C.sub.2 H.sub.5                                                                      --                                               CH.sub.3    CH.sub.3  C.sub.2 H.sub.5                                                                      --                                               ______________________________________                                    

EXAMPLE 11 Preparation of furo[3,2-b]pyridine-5,6-dicarboxylic acidanhydride ##STR31##

Furo[3,2-b]pyridine-5,6-dicarboxylic acid (3.3 g, 0.0159 mol) in aceticanhydride (100 mL) is heated to 70°-80° C. for six hours. The reactionmixture is cooled, filtered and the solid is washed with ether to give3.01 (100%) of crude furo[3,2-b]pyridine-5,6-dicarboxylic acidanhydride.

Utilizing the above procedure and substituting the appropriatefuro[3,2-b]pyridine-5,6-dicarboxylic acid yields the compoundsillustrated below.

    ______________________________________                                        Y              Z      mp ° C.                                          ______________________________________                                        H              H      --                                                      H              Cl     --                                                      CH.sub.3       H      --                                                      H              CH.sub.3                                                                             --                                                      C.sub.2 H.sub.5                                                                              H      --                                                      H              C.sub.2 H.sub.5                                                                      --                                                      CH.sub.3       CH.sub.3                                                                             --                                                      ______________________________________                                    

EXAMPLE 12 Preparation of5-[(1-carbamoyl-1,2-dimethylpropyl)-carbamoyl]furo[3,2-b]pyridine-6-carboxylicacid and5-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)furo-[3,2-b]pyridine-6-carboxylicacid ##STR32##

Furo[3,2-b]pyridine-5,6-dicarboxylic acid anhydride (3.01 g, 0.015 mol)is suspended in THF (100 mL) to which 2-amino-2,3-dimethylbutyramide(2.3 g, 0.018 mol) is added. After stirring for 20 hours, the solutionis stripped to an oily solid which dissolves in a water/dilute sodiumhydroxide solution. The alkaline solution is extracted with methylenechloride, and then acidified and reextracted with methylene chloride buton stirring only minute traces of material is isolated. The water layeris concentrated to an oily solid which is dissolved in ethanol, filteredand concentrated to a purple gum which is predominantly the crudeproduct,5-[(1-carbamoyl-1,2-dimethylpropyl)carbamoyl]furo[3,2-b]pyridine-6-carboxylicacid and is used without further purification to prepare the final2-imidazolin-2-yl product by dissolving it in 10% sodium hydroxidesolution (40 mL) and warming at 80° C. for three hours. On cooling thereaction is acidified and a small amount of solid precipitated out andwas filtered off. Concentration of mother liquors gives a second crop,which is collected and combined with the first crop. Purification iseffected by taking half of the material and separating on silica gelpreparative glass plates as bands. The slower running band usingmethylene chloride:ethyl acetate:chloroform:methanol 1:1:1:1 as eluant,affords the desired 2-imidazolin-2-yl product, mp 214°-223° C. (dec),Esters may then be prepared by the procedures described in Example 20.

Utilizing the above procedure and substituting the appropriatefuro[3,2-b]pyridine-5,6-dicarboxylic anhydride yields the compoundsillustrated below.

    ______________________________________                                         ##STR33##                                                                    Y             Z      mp °C.                                            ______________________________________                                        H             H      214-223 (dec)                                            H             Cl     --                                                       CH.sub.3      H      --                                                       H             CH.sub.3                                                                             --                                                       C.sub.2 H.sub.5                                                                             H      --                                                       H             C.sub.2 H.sub.5                                                                      --                                                       CH.sub.3      CH.sub.3                                                                             --                                                       ______________________________________                                    

EXAMPLE 13 Preparation of dimethylthieno[2,3-b]pyridine-5,6-dicarboxylate ##STR34##

A Vilsmeier reagent is prepared by adding dropwise, with stirring,phosphorus oxychloride (40.29 g, 0.26 mol) to a cooled (10° C.) solutionof DMF (19.0 g, 0.26 mol) in 1,2-dichloroethane (40 mL) in an N₂atmosphere. This reagent is stirred at room temperature for one hour and45 minutes. Dimethyl-2-thienyl-aminobutenedioate (63.4 g, 0.26 mol)dissolved in 1,2-dichloroethane (300 mL) is added dropwise to theVilsmeier reagent at 7°-10° C. The reaction temperature is raised toroom temperature for 15 minutes, then to reflux for 12 hours. The cooledreaction mixture is concentrated and the residue chromatographed on asilica gel column with ethyl acetate-hexane, affordingdimethylthieno[2,3-b]pyridine-5,6-dicarboxylate (29 g, 45%) as a solid.

Utilizing the above procedure and substituting the appropriatedimethyl-2-thienylaminobutenedioate yields the compounds illustratedbelow.

    ______________________________________                                         ##STR35##                                                                    Y             Z      mp °C.                                            ______________________________________                                        CH.sub.3      H      80-82                                                    H             H      80-81                                                    H             CH.sub.3                                                                             --                                                       CH.sub.3      CH.sub.3                                                                             --                                                       H             C.sub.6 H.sub.5                                                                      --                                                       C.sub.6 H.sub.5                                                                             H      --                                                       CF.sub.3      H      --                                                       (CH.sub.2).sub.4   118-121.5                                                  ______________________________________                                    

EXAMPLE 14 Preparation of dimethyl3-bromothieno[2,3-b]pyridine-5,6-dicarboxylate ##STR36##

Bromine (0.33, 0.00206 mol) in acetic acid (8 mL) is added to a stirredsolution of dimethyl-thieno[2,3-b]pyridine-5,6-dicarboxylate (0.5 g,0.00187 mol) in acetic acid containing sodium acetate (0.31 g, 0.00377mol) at 40° C. The reaction mixture is heated at 75° C. for 18 hours.Evaluation of the mixture by tlc (silica gel) indicated incompletereaction. Additional bromine (0.33 g) in acetic acid and sodium acetate(0.31 g) is added and heating at 75° C. continued for six hours. Thereaction mixture is diluted with water and extracted into ethyl acetate.The separated organic layer is dried over anhydrous MgSO₄, filtered, andthe filtrate concentrated to an oil which solidifies on standing.Crystallization of the crude product from ethyl acetate-hexanes yieldsthe dimethyl 3-bromothieno-[2,3-b]pyridine-5,6-dicarboxylate as whiteneedles mp 86°-87.5° C.

This compound may be readily converted to a variety ofsubstituted-thieno[2,3-b]pyridine compounds as illustrated below, whileelectrophilic substitution such as nitration or halogenation yieldsadditional compounds listed below.

    ______________________________________                                         ##STR37##                                                                    Y           Z          mp °C.                                          ______________________________________                                        H           H          --                                                     H           Cl         104-110                                                H           Br           86-87.5                                              H           I          --                                                     H           F          --                                                     H           CN         --                                                     H           SCH.sub.3  --                                                     H           OCH.sub.3  --                                                     H           N(CH.sub.3).sub.2                                                                        --                                                     H           OCHF.sub.2 --                                                     H           NO.sub.2   --                                                     H           CHO        --                                                     H           CH.sub.2 Cl                                                                              --                                                     CH.sub.3    H          80-82                                                  H           CH.sub.3   oil                                                    Cl          H          --                                                     Cl          Cl         84-89                                                  CH.sub.3    CH.sub.3   --                                                     H           SO.sub.2 N(CH.sub.3).sub.2                                                               --                                                     (CH.sub.2).sub.4   118.5-121.5                                                (CH).sub.4         --                                                         (CH.sub.2).sub.3   --                                                         C.sub.6 H.sub.5                                                                           H          --                                                     H           C.sub.6 H.sub.5                                                                          --                                                     H           OC.sub.6 H.sub.5                                                                         --                                                     CF.sub.3    H          --                                                     H           SC.sub.6 H.sub.5                                                                         --                                                     H           CF.sub.3   --                                                     C.sub.2 H.sub.5                                                                           H          --                                                     H           C.sub.2 H.sub.5                                                                          --                                                     ______________________________________                                    

EXAMPLE 15 Preparation of thieno[2,3-b]pyridine-5,6-dicarboxylic acid##STR38##

A solution containing dimethyl thieno[2,3-b]-pyridine-5,6-dicarboxylate(27.75 g, 0.11 mol) and potassium hydroxide (30.98 g, 0.55 mol) inmethanol (200 mL) under a N₂ atmosphere is heated at reflux for twohours. The reaction mixture is cooled and sufficient water added todissolve any solids present before evaporating the mixture to dryness.The resulting solid is dissolved in a minimum volume of water, cooled inan ice bath and acidified with concentrated H₂ SO₄ to pH˜1.Thieno[2,3-b]pyridine-5,6-dicarboxylic acid is filtered off and driedovernight to give 23.36 g mp 272°-275° C.

Utilizing the above procedure and substituting the appropriatesubstituted dialkylthieno[2,3-b]pyridine-5,6-dicarboxylate yields thecompounds illustrated below.

    ______________________________________                                         ##STR39##                                                                    Y           Z          mp °C.                                          ______________________________________                                        H           H          272-275                                                H           Cl         >300                                                   H           Br         >315                                                   H           I          --                                                     H           F          --                                                     H           CN         --                                                     H           SCH.sub.3  --                                                     H           OCH.sub.3  --                                                     H           N(CH.sub.3).sub.2                                                                        --                                                     H           OCHF.sub.2 --                                                     H           NO.sub.2   --                                                     H           CHO        --                                                     H           CH.sub.2 Cl                                                                              --                                                     H           CH.sub.3   180-183 (dec)                                          CH.sub.3    H          --                                                     Cl          H          --                                                     Cl          Cl         --                                                     CH.sub.3    CH.sub.3   --                                                     C.sub.6 H.sub.5                                                                           H          --                                                     H           SO.sub.2 N(CH.sub.3).sub.2                                                               --                                                     (CH.sub.2).sub.3   --                                                         (CH.sub.2).sub.4   280-290                                                    (CH).sub.4         --                                                         H           OC.sub.6 H.sub.5                                                                         --                                                     H           C.sub.6 H.sub.5                                                                          --                                                     CF.sub.3    H          --                                                     H           CF.sub. 3  --                                                     H           SC.sub.6 H.sub.5                                                                         --                                                     C.sub.2 H.sub.5                                                                           H          --                                                     H           C.sub.2 H.sub.5                                                                          --                                                     ______________________________________                                    

EXAMPLE 16 Preparatiaon of thieno[2,3-b]pyridine-5,6-dicarboxylicanhydride ##STR40##

Acetic anhydride (37.4 g, 0.366 mol) is added to a stirred suspension ofthieno[2,3-b]pyridine-5,6-dicarboxylic acid (21.52 g, 0.096 mol) indimethoxyethane (175 mL) in an inert N₂ atmosphere. Upon addition ofpyridine (16.78 g, 0.21 mol) at room temperature an exotherm to 45° C.is observed and a homogeneous solution results. The reaction mixture isthen stirred at room temperature and the resulting solid filtered off,washed with ether and air dried to give 14.8 g (75%) ofthieno[2,3-b]pyridine-5,6-dicarboxylic acid anhydride.

Utilizing the above procedure and substituting the appropriatesubstituted thieno[2,3-b]pyridine-5,6-dicarboxylic acid yields thecompounds illustrated below.

    ______________________________________                                         ##STR41##                                                                    Y           Z          mp °C.                                          ______________________________________                                        CH.sub.3    H          176-180                                                H           Br         228.5-231                                              H           Cl         230-300                                                                       (slow dec)                                             H           H          210-213                                                H           I          --                                                     H           F          --                                                     H           CN         --                                                     H           SCH.sub.3  --                                                     H           N(CH.sub.3).sub.2                                                                        --                                                     H           NO.sub.2   --                                                     H           CHO        --                                                     H           CH.sub.2 Cl                                                                              --                                                     H           CH.sub.3   --                                                     Cl          H          --                                                     Cl          Cl         --                                                     CH.sub.3    CH.sub.3   --                                                     C.sub.6 H.sub.5                                                                           H          --                                                     H           SO.sub.2 N(CH.sub.3).sub.2                                                               --                                                     (CH.sub.2).sub.3   --                                                         (CH.sub.2).sub.4   220-222                                                    (CH).sub.4         --                                                         H           C.sub.6 H.sub.5                                                                          --                                                     H           OC.sub.6 H.sub.5                                                                         --                                                     CF.sub.3    H          --                                                     H           CF.sub.3   --                                                     H           OCHF.sub.2 --                                                     H           SC.sub.6 H.sub.5                                                                         --                                                     H           OCH.sub.3  --                                                     C.sub.2 H.sub.5                                                                           H          --                                                     H           C.sub.2 H.sub.5                                                                          --                                                     ______________________________________                                    

EXAMPLE 17 Preparation of6-[(1-carbamoyl-1,2-dimethylpropyl)-carbamoyl]thieno[2,3-b]pyridine-5-carboxylicacid ##STR42##

2-Amino-2,3-dimethylbutyramide (9.84 g, 0.076 mol) is added to a stirredsuspension of thieno-[2,3-b]pyridine-5,6-dicarboxylic acid anhydride(14.8 g, 0.072 mol) in THF under an inert atmosphere of N₂ at roomtemperature. The dark solution is stirred at room temperature overnightand the resulting solid filtered off, washed with THF and air dried togive 17.35 g (72%) of6-[(1-carbamoyl-1,2-dimethylpropyl)carbamoyl]thieno[2,3-b]pyridine-5-carboxylicacid.

Utilizing the above procedure and substituting the appropriatesubstituted thieno[2,3-b]pyridine-5,6-dicarboxylic acid anhydride yieldsthe compounds illustrated below.

    ______________________________________                                         ##STR43##                                                                    Y            Z          mp °C.                                         ______________________________________                                        CH.sub.3     H          207-208                                               H            Br         176-178                                               H            Cl         156-158                                               H            H          --                                                    H            I          --                                                    H            F          --                                                    H            CN         --                                                    H            SCH.sub.3  --                                                    H            OCH.sub.3  --                                                    H            N(CH.sub.3).sub.2                                                                        --                                                    H            NO.sub.2   --                                                    H            CHO        --                                                    H            CH.sub.2 Cl                                                                              --                                                    H            CH.sub.3   --                                                    Cl           H          --                                                    Cl           Cl         --                                                    CH.sub.3     CH.sub.3   --                                                    C.sub.6 H.sub.5                                                                            H          --                                                    H            SO.sub.2 N(CH.sub.3).sub.2                                                               --                                                    (CH.sub.2).sub.3    --                                                        (CH.sub.2).sub.4    solid                                                     (CH).sub.4          --                                                        H            C.sub.6 H.sub.5                                                                          --                                                    H            OC.sub.6 H.sub.5                                                                         --                                                    CF.sub.3     H          --                                                    H            OCHF.sub.2 --                                                    H            CF.sub.3   --                                                    H            SC.sub.6 H.sub.5                                                                         --                                                    C.sub.2 H.sub.5                                                                            H          --                                                    H            C.sub.2 H.sub.5                                                                          --                                                    ______________________________________                                    

EXAMPLE 18 Preparation of6-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)thieno[2,3-b]pyridine-5-carboxylicacid ##STR44##

6-[(1-Carbamoyl-1,2-dimethylpropyl)carbamoyl]thieno[2,3-b]pyridine-5-carboxylicacid (17.35 g, 0.052 mol) is added to water (225 mL) containing sodiumhydroxide (10.35 g, 0.26 mol). The resulting basic solution is heated at80° C. for two hours and 45 minutes, cooled in an ice-water bath andacidified with 6N H₂ SO₄. The product6-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)thieno[2,3-b]pyridine-5-carboxylicacid is filtered off, washed with water and air dried yielding 1.54 g,70.3%, mp 221°-223° C.

EXAMPLE 19 Preparation of5H-Imidazo[1',2':1,2]pyrrolo[3,4-b]thieno[3,2-e]pyridine-3(2H),5-dione,2-isopropyl-2-methyl ##STR45##

Dicyclohexylcarbodiimide (1.07 g, 0.005 mol) in methylene chloride (20mL) is added dropwise to a stirred methylene chloride (30 mL) suspensionof6-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)thieno-[2,3-b]-5-carboxylicacid (1.5 g, 0.0047 mol) under an N₂ atmosphere. After stirring thereaction mixture for 16 hours, it was clarified by filtration,concentrated to dryness and the resulting material purified by columnchromatography on silica gel eluting with acetonitrile/methylenechloride (1/2). The solid product was crystallized from toluene to givethe pure 3,5-dione as white crystals mp 214.5°-216.5° C.

EXAMPLE 20 Preparation of 2-propynyl6-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)thieno[2,3-b]pyridine-5-carboxylate##STR46##

Sodium hydride (2.4 g, 60%, 0.126 mol) is added to the 3,5-dione (0.9 g,0.003 mol) in propargyl alcohol (25 mL) at 10° C. under an inert N₂atmosphere. The reaction mixture is stirred at room temperature for 60hours and then neutralized with a saturated ammonium chloride solution.The resulting mixture is concentrated on a rotary evaporator, dilutedwith water and extracted with ethyl acetate. The organic layer isseparated, dried over anhydrous MgSO₄ and concentrated to dryness.

Purification of the product by column chromatography on silica gel withmethylene chloride/acetonitrile (85/15) yields 2-propynyl6-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)pyridine-5-carboxylate,which after crystallization from toluene has a mp 188°-189.5° C.

Utilizing the procedures of Examples 18, 19 and 20 and substituting theappropriate thieno [3,2-b]pyridine or thieno [2,3-b]pyridine compounds,yields the compounds illustrated below.

    ______________________________________                                         ##STR47##                                                                    Y     Z           R.sub.3        mp °C.                                ______________________________________                                        H     H           CH.sub.3       215-217                                      H     H           H              220-223.5                                                                     (dec)                                        H     H           CH.sub.2 CCH   188-189.5                                    H     H                                                                                          ##STR48##     140-142                                      H     H                                                                                          ##STR49##     108-110                                      CH.sub.3                                                                            H           H              225.5-227.5                                  H     Br          H              274-276                                      H     Cl          H              266-267                                      H     NO.sub.2    CH.sub.3       201-202.5° C.                         H     NO.sub.2    H              260 (dec)                                    Cl    H           H              --                                           Cl    Cl          H              --                                           H     CH.sub.3    H              --                                           H     N(CH.sub.3).sub.2                                                                         H              --                                           H     SCH.sub. 3  H              --                                           H     OCH.sub.3   H              --                                           H     OCHF.sub.2  H              --                                           CH.sub.3                                                                            CH.sub.3    H              --                                           H     CN          H              --                                           H     SO.sub.2 N(CH.sub.3).sub.2                                                                H              --                                           C.sub.6 H.sub.5                                                                     H           H              --                                           H     C.sub.6 H.sub.5                                                                           H              --                                           (CH.sub.2).sub.3                                                                            H              --                                               (CH.sub.2).sub.4                                                                            H              --                                               (CH.sub.2).sub.4                                                                            H              --                                               H     OC.sub.6 H.sub.5                                                                          H              --                                           CF.sub.3                                                                            H           H              --                                           C.sub.2 H.sub.5                                                                     H           H              --                                           H     C.sub.2 H.sub.5                                                                           H              --                                           H     I           H              --                                           H     F           H              --                                           H     CHO         H              --                                           H     CH.sub.2 Cl H              --                                           H     CF.sub.3    H              --                                           H     SC.sub.5 H.sub.6                                                                          H              --                                           ______________________________________                                    

    ______________________________________                                         ##STR50##                                                                    Y      Z            R.sub.3       mp °C.                               ______________________________________                                        H      H            H             242-244                                     H      Cl           H             238-239                                     H      Br           H             226-227                                     H      H                                                                                           ##STR51##    156-157                                     Cl     H            H             266-267                                     Cl     I            H             --                                          H      CH.sub.3     H             --                                          H      F            H             --                                          CH.sub.3                                                                             H            H             --                                          Cl     Cl           H             --                                          H      NO.sub.2     H             --                                          H      N(CH.sub.3).sub.2                                                                          H             --                                          H      SCH.sub.3    H             --                                          H      OCH.sub.3    H             --                                          CH.sub.3                                                                             CH.sub.3     H             --                                          H      CHO          H             --                                          H      OCHF.sub.2   H             --                                          H      CN           H             --                                          H      SO.sub.2 N(CH.sub. 3).sub.2                                                                H             --                                          C.sub.6 H.sub.5                                                                      H            H             --                                          H      C.sub.6 H.sub.5                                                                            H             --                                          (CH.sub.2).sub.3    H             --                                          (CH.sub.2).sub.4    H             --                                          (CH.sub.2).sub.4    H             --                                          H      OC.sub.6 H.sub.5                                                                           H             --                                          CF.sub.3                                                                             H            H             --                                          H      CF.sub.3     H             --                                          C.sub.2 H.sub.5                                                                      H            H             --                                          H      C.sub.2 H.sub.5                                                                            H             --                                          H      CH.sub.2 Cl  H             --                                          H      SC.sub.6 H.sub.5                                                                           H             --                                          ______________________________________                                    

EXAMPLE 21 Preparation of methyl6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-3-nitrothieno[2,3-b]pyridine-5-carboxylate##STR52##

Methyl6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)thieno[2,3-b]pyridine-5-carboxylate(3.94 g, 0.0119 mol) is dissolved in 200 mL concentrated H₂ SO₄ at roomtemperature. While cooling to 3° C. in an ice bath, 1.5 mL (0.024 mol)concentrated HNO₃ is added, then the mixture is allowed to warm to roomtemperature. After three hours, the reaction mixture is poured onto ice,neutralized with solid NaHCO₃ to pH 6 and is extracted with methylenechloride. The extract is filtered, then dried over sodium sulfate,refiltered and concentrated to a yellow solid weighing 4.33 g (97%),which upon crystallization from methanol water has mp 201°-202.5° C.

EXAMPLE 22 Preparation of6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-3-nitrothieno[2,3-b]pyridine-5-carboxylicacid ##STR53##

The ester (1.0 g, 0.00266 mol) from Example 21 is stirred in 100 mLmethanol and 10 mL 10% sodium hydroxide solution for 24 hours. Water (25mL) is added and the methanol removed in vacuo. Acidification of theaqueous layer gives a brown precipitate which upon filtration andcrystallization from methanol-water has mp 260° C.

EXAMPLE 23 Preparation of diethyl5-acetyl-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate ##STR54##

Sodium acetate (30 g, 0.37 mol) is added to a stirred mixture ofdiethyl(ethoxymethylene)oxalacetate (87 g, 0.36 mol) and acetoacetamide(36 g, 0.36 mol) in absolute ethanol (300 mL). After stirring thereaction mixture for 30 minutes, the ethanol is distilled off underreduced pressure, the residue acidified to pH 2 with dilute aqueoushydrochloric acid and the resulting solid filtered off. Crystallizationfrom an ethanol-water mixture affords diethyl5-acetyl-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate as crystals mp101°-110° C.

EXAMPLE 24 Preparation of isobutyryl acetonitrile ##STR55##

NaH (61.55 g of 60% dispersion, 1.54 mol) is added to 650 mL anhydrousTHF under N₂. The suspension is heated to reflux. Methyl isobutyrate(100 g, 98 mol) and acetonitrile (63.16 g, 1.54 mol) are mixed in 140mLs anhydrous THF and added dropwise over one hour to the refluxingsuspension. The resulting solution is refluxed for 16 hours. Enoughwater is added to the reaction mixture to dissolve the salt that isformed. The THF is removed in vacuo, and the basic aqueous solution isextracted with ether, then acidified to pH 4 with concentrated HCl. Thesolution is extracted with ether. The extracts are washed with brine anddried over anhydrous MgSO₄, filtered and the solvent is removed invacuo, giving 97.25 g, (89.4%) of the title product an orange oil.

EXAMPLE 25 Preparation ofdiethyl-5-(2-methylpropionyl)-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate##STR56##

Isobutyl acetonitrile (50 g, 0.45) 24 anddiethyl(ethoxymethylene)oxalacetate (110 g, 0.45 mol) are dissolved inabsolute ethanol and then is added sodium acetate (36.9 g, 0.45 mol) andone drop of piperidine. After 12 hours, the mixture is concentrated,acidified with dilute hydrochloric acid then extracted with methylenechloride. The extracts are concentrated and recrystallized to give thetitle product as a white solid 21.7 g (19.5%) mp 116°-118° C.

EXAMPLE 26 Preparation of diethyl5-(bromoacetyl)-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate ##STR57##

Bromine (8.0 g, 0.050 mol) in 48% HBr is added dropwise to a stirredsolution of diethyl-5-acetyl-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate(14.05 g, 0.05 mol) in 48% HBr (200 mL). Upon completion of this bromineaddition the reaction mixture is poured onto ice (200 g) and the mixtureis stirred until the ice has melted. The crude product is collected byfiltration and crystallized twice from an ethyl acetate-hexane mixture(1/2) affording diethyl5-(bromoacetyl)-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate with mp141°-142° C.

Utilizing the the above procedure using diethyl2-methylpropionyl-2-pyridone-dicarboxylate yields diethyl5-(2-bromo-2-methylpropionyl)-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate,mp 124°-126° C.

EXAMPLE 27 Preparation of diethyl5-(2-bromo-1-hydroxyethyl)-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylateand diethyl 2,3-dihydro-3-hydroxy-furo[2,3-b]pyridine-5,6-dicarboxylate##STR58##

Sodium borohydride (2.54 g, 0.066 mol) is added in portions over a 30minute period to a stirred suspension of diethyl5-(bromoacetyl)-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate (57.2 g,0.159 mol) at 10°-20° C. Upon completion of the sodium borohydrideaddition, the reaction mixture is stirred while attaining roomtemperature. Ice (100 g) is added and the mixture stirred until the icehas melted. The mixture is then concentrated in vacuo and the residuecrystallized twice from an ethyl acetate-hexane mixture to give purediethyl5-(2-bromo-1-hydroxyethyl)-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylatemp 134°-138° C. Stirring this compound with triethylamine (1.0 mL/g ofsolid) in methylene chloride for one hour, followed by washing theorganic solution with dilute hydrochloric acid, water, brine and dryingover anhydrous MgSO₄ yields the crude furo[2,3-b]pyridine as an oil uponremoving the solvent in vacuo. Crystallization from acyclohexane-toluene mixture affords pure diethyl2,3-dihydro-3-hydroxy-furo[2,3-b]pyridine-5,6-dicarboxylate mp 73°-77°C.

EXAMPLE 28 Preparation of diethyl2,3-dihydro-3-methoxyfuro[2,3-b]pyridine-5,6-dicarboxylate ##STR59##

Sodium hydride, 60% dispersion in mineral oil (2.05 g, 0.0512 mol) andiodomethane (7.9 mL, 0.128 mol) are added to a solution of the hydroxydiester of Example 27 (12.00 g, 0.0427 mol) in tetrahydrofuran (400 mL)under N₂. After stirring overnight at room temperature, the reaction isheated to 50° C. under a stream of N₂ to remove excess iodomethane. Thereaction is then cooled, filtered, stripped and chromatographed oversilica gel. Eluting with hexane/ethyl acetate (4:1) gives the product asa yellow oil in 57.3% yield. Calcd. for C₁₄ H₁₇ NO₆ ; C, 56.94; 4, 5.80,N, 4.74. Found: C, 56.93; H, 5.59; N, 4.83.

EXAMPLE 29 Preparation of diethyl furo[2,3-b]pyridine-5,6-dicarboxylate##STR60##

A xylene solution of the hydroxy-furo compound obtained in Example 23,(3.7 g) containing para-toluene sulfonic acid (0.01 g) is heated atreflux for two hours. The solution is cooled and the xylene solutiondecanted off. The residue is extracted with ether and the extractscombined with the xylene. Distillation of the solvents gives a yellowsolid which is crystallized from a cyclohexane-toluene mixture to givepure diethyl furo[2,3-b]pyridine-5,6-dicarboxylate mp 66°-77° C.

EXAMPLE 30 Preparation of dimethyl2-methyl-furo[2,3-b]pyridine-5,6-dicarboxylate ##STR61##

Propyne (3.0 mLs, 0.045 mol) is condensed in a graduated cylinder in adry ice/acetone bath and added to a stirred suspension of dimethyl1,6-dihydro-5-iodo-6-oxo-2,3-pyridinedicarboxylate (13.48 g, 0.04 mol),cuprous iodide (0.38 g, 0.002 mol) and bis(triphenylphosphine)palladiumII) chloride (2.81 g, 0.004 mol) in 150 mLs DMSO and 50 mLstriethylamine at 10° C. After addition of the propyne the reactionmixture is stirred at room temperature for 60 hours. Water is added andthe mixture is extracted with ethyl acetate. The ethyl acetate solutionis washed with water and dried over anhydrous MgSO₄, then concentratedin vacuo to give a mixture of materials. The crude product is isolatedby flash column chromatography using 9:1 methylene chloride:ethylacetate. The fractions containing the title product are concentrated invacuo and the residue is recrystallized from cyclohexane to give thepure compound mp 115°-118° C.

Utilizing the above procedure and substituting the appropriatesubstituted acetylene yields the compounds illustrated below.

    ______________________________________                                         ##STR62##                                                                           R     mp °C.                                                    ______________________________________                                               C.sub.2 H.sub.5                                                                     147-149                                                                 Phenyl                                                                              152-153                                                          ______________________________________                                    

EXAMPLE 31 Preparation of diethyl2,3-dihydro-3,3-dimethylfuro[2,3-b]pyridine-5,6-dicarboxylate ##STR63##

The 5-(2-bromo-2-methylpropy ketone diester of Example 26 (20 g, 0.052mol) is dissolved in 200 mL absolute ethanol and 3.0 g sodiumborohydride (0.078 mol) is added at 0° C., the temperature is thenallowed to rise gradually to 15° C. After the mixture is stirred for oneadditional hour, the ethanol is removed in vacuo. The solidified mass istreated with water and extracted with methylene chloride. The organicextract is then washed with water and a saturated sodium chloridesolution, dried and concentrated. The residue, weighing 12 g isredissolved in xylene and 1.0 g p-toluenesulfonic acid is added. Thesolution is refluxed for 12 hours then cooled. The xylene solution isdecanted and the residue washed with several portions of ether. Thecombined organic solutions are concentrated then chromatographed with9:1 methylene chloride/ethyl acetate to obtain 3.2 g of the oily diester(21%); mass spectrum M+1/e=294.

From a later chromatographic fraction is obtained 1.4 g of2,2-dimethyl-3-hydroxyfuro[2,3-b]pyridine-5,6-dicarboxylate (11.5%).

EXAMPLE 32 Preparation of diethyl3-bromofuro[2,3-b]pyridine-5,6-dicarboxylate ##STR64##

The diester of Example 29 (6.0 g, 0.0228 mol) is dissolved in 200 mLmethylene chloride containing 4.6 g sodium acetate, and bromine is added(7.3 g, 0.0556 mol) at reflux. Following the addition, the mixture wasstirred for 15 minutes at reflux, then cooled, washed with aqueoussodium bisulfite, dried with sodium sulfate and filtered. The filtratewas stripped to 8.8 g of the crude dibromo compound which wasredissolved in methylene c hloride and treated with 3.16 g DBU (0.021mol) at room temperature for 30 minutes. The mixture was thenconcentrated in vacuo, and chromatographed over silica gel withhexane-ethylacetate to give 7.1 g (90%) of the diethyl3-bromofuro[2,3-b]pyridine-5,6-dicarboxylate mono bromo diester mp49.5°-52° C.

EXAMPLE 33 Preparation of diethyl2,3-dibromofuro[2,3-b]pyridine-5,6-dicarboxylate ##STR65##

Sodium acetate (2.40 g, 0.0292 mol) and bromine (7.5 mL, 0.146 mol) areadded to a solution of diethyl3-bromofuro[2,3-b]pyridine-5,6-dicarboxylate (5.00 g, 0.0146 mol) inmethylene chloride (150 mL). The mixture is stirred at room temperaturefor four days then washed with aqueous sodium bisulfate to removeunreacted bromine. The aqueous solution is then back extracted withmethylene chloride. The organic solution is combined, dried over sodiumsulfate and filtered. To the filtrate is added1,8-diazabicyclo-[5.4.0]undec-7-ene (4.4 mL, 0.032 mol), and the mixtureis stirred at room temperature for one hour. The solution is thenconcentrated in vacuo. The residue is chromatographed over silica geleluting with 20% ethyl acetate in hexane, yielding the crude2,3-dibromofuro[2,3-b]pyridine as a white solid in 95% yieldsrecrystallization from a methylene chloride-hexane mixture affordsdiethyl 2,3-dibromofuro[2,3-b]pyridine-5,6-dicarboxylate mp 96°-98° C.in 75.9% recrystallized yield.

EXAMPLE 34 Preparation of diethyl3-trifluoromethylfuro[2,3-b]pryidine-5,6-dicarboxylate ##STR66##

To a solution of sodium trifluoroacetate (0.0234 mol) inN-methylpyrrolidone (50 mL) is added 3-bromofuropyridine of Example 32(2.02, 0.00585 mol) and cuprous iodide (2.2 g, 0.0119 mol). The mixtureis heated to 160° C. for three hours under N₂, cooled to roomtemperature, treated with EtOAc (100 mL) and hexene (100 mL), andfiltered. The filtrate is washed with H₂ O (4×200 mL), dried over Na₂SO₄ and stripped to an oil which is chromatographed over silica gel withhexane-ETOAc (7:3) elution. The product is collected as a pale yellowsolid; mp 50°-55° C.

EXAMPLE 35

Preparation of furo[2,3-b]pyridine-5,6-dicarboxylic acid ##STR67##

Potassium hydroxide (5.60 g, 85%, 0.087 mol) in water (5 mL) is added toa stirred suspension of diethyl furo[2,3-b]pyridine-5,6-dicarboxylate(9.3 g, 0.035 mol) in absolute ethanol (100 mL). The reaction mixture isheated at 60° C. for one hour, then cooled and anhydrous acetone added.The precipitate is filtered off, dried, suspended in dry acetone andtreated with hydrogen chloride to adjust to a pH of 2. Crystallizationof the isolated solids from an ethyl acetate-acetone mixture affordsfuro[2,3-b]pyridine-5,6-dicarboxylic acid mp 189°-192° C.

EXAMPLE 36 Preparation of furo[2,3-b]pyridine-5,6-dicarboxylic anhydride##STR68##

Furo[2,3-b]pyridine-5,6-dicarboxylic acid (6.7 g, 0.032 mol) is heatedat 60° C. for 30 minutes in acetic anhydride (150 mL). The reactionmixture is cooled to room temperature and concentrated in vacuo and theresidue triturated with cyclohexane-ether (5:1), filtered off and driedto give 5.35 g furo[2,3-b]pyridine-5,6-dicarboxylic acid anhydride.

EXAMPLE 37 Preparation of6-[(1-carbamoyl-1,2-dimethylpropyl)carbamoyl]-furo[2,3-b]pyridine-5-carboxylicacid ##STR69##

2-Amino-2,3-dimethylbutyramide (2.1 g, 0.016 mol) is added to a stirredsuspension of furo[2,3-b]pyridine-5,6-dicarboxylic acid anhydride (3.0g, 0.016 mol) in tetrahydrofuran (7.5 mL) and the mixture allowed tostir at room temperature for 16 hours. The reaction mixture is thenstirred at 60° C. for one hour, cooled to room temperature, ether added,and the solid filtered off and dried to give 5 g of6-[(1-carbamoyl-1,2-dimethylpropyl)carbamoyl]furo[2,3-b]pyridine-5-carboxylicacid mp 192°-196° C. (dec).

EXAMPLE 38 Preparation of6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[2,3-b]pyridine-5-carboxylicacid ##STR70##

A solution containing6-[(1-carbamoyl-1,2-dimethylpropyl)carbamoyl]furo[2,3-b]pyridine-5-carboxylicacid (3.8 g, 0.012 mol) in aqueous sodium hydroxide 2.4 g, 0.06 mol) inwater (40 mL) is stirred at 65° C. for three hours. The reaction mixtureis then heated at 75° C. for one hour, allowed to cool, poured into ice,acidified to pH 2-3 and the resulting solid filtered off and dried.Crystallization from an acetone-methanol mixture affords pure6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[2,3-b]pyridine-5-carboxylicacid mp 237°-244° C.

EXAMPLE 39 Preparation of6-[4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-3-nitrofuro[2,3-b]pyridine-5-carboxylicacid ##STR71##

Nitryl hexafluorophosphate (0.75 g, 0.00391 mol) is added to asuspension of6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-furo[2,3-b]pyridine-5-carboxylicacid (1.07 g, 0.00355 mol) in sulfolane (63 mL) under nitrogen. Thetemperature of the reaction is maintained between 64° C. and 85° C. forthree days during which time the solids dissolve. The mixture is cooledto 30° C. and chromatographed over silica gel. Elution with 1:1 hexaneto ethyl acetate removes the sulfolane. Elution with 1% to 10% methanolin methylene chloride followed by recrystallization from acetone-hexaneyields6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-3-nitro-furo[2,3-b]pyridine-5-carboxylicacid, mp 220°-237° C.

EXAMPLE 40 Preparation of2-isopropyl-2-methyl-5H-furo[2,3-b]imidazo[2',1':5,1]pyrrolo[3,4-b]pyridine-3(2H),5-dione##STR72##

To a suspension of6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-furo[2,3-b]-pyridine-5-carboxylicacid (11.7 g, 0.039 mol) in 100 mL dimethoxyethane (DME) is added 7.3 mLacetic anhydride and 3.9 mL pyridine. After stirring 24 hours at roomtemperature, the solids are filtered and washed with ether and themother liquor is concentrated by adding xylene to aid removal ofpyridine. The residue is triturated with ether to obtain solids whichare combined with the first crop to give 11.1 g (100%) of product.Recrystallization from 2:1 ethyl acetate-hexane gives an analyticalsample mp 193°-205° C.

EXAMLE 41 Preparation of methyl6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-furo[2,3-b]pyridine-5-carboxylate##STR73##

The compound prepared in Example 40 (10.5 g, 0.037 mol) is suspended in150 mL absolute methanol and 4.0 g sodium methoxide is added. Afterstirring for 72 hours at room temperature the mixture is poured onto icecontaining acetic acid to maintain the pH at 3-4. A white solid formsand is filtered yielding 9.8 g (84%) of the title compound with mp134°-137° C.

EXAMPLE 42 Preparation of methyl3-chloro-6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-furo[2,3-b]pyridine-5-carboxylate##STR74##

The methyl ester described in Example 40 is dissolved (1.4 g, 4.4 mmol)in 20 mL acetic acid and sodium acetate (1.0 g, 12.2 mmol) is added.Gaseous chlorine is passed into the stirred solution for two hoursduring which time the temperature reaches 40° C. After cooling andpouring onto 50 g ice, the mixture is extracted with ethyl acetate,washed with distilled water then with saturated sodium carbonatesolution. The organic layer is then concentrated to a foam, redissolvedin 20 mL methylene chloride and treated with 10 mLdiazabicyclo-[5.4.0]undec-5-ene (DBU). After ten minutes, the mixture istreated with 20 mL cold dilute hydrochloric acid. The methylene chloridelayer is removed, dried over anhydrous magnesium sulfate. The solutionis then passed through a one-quarter inch pad of silica gel andconcentrated in vacuo. Recrystallization from hexane-ethyl acetate gives0.85 g (57%) of the 3-chloro compound mp 150°-156° C.

EXAMPLE 43 Preparation of3-chloro-6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-furo[2,3-b]pyridine-5-carboxylicacid ##STR75##

The ester from Example 42 (0.55 g, 1.157 mmol) is dissolved in 10 mL 95%ethanol and 0.28 g 50% sodium hydroxide solution is added. After onehour the mixture is treated with 10% hydrochloric acid to pH 2, and theproduct separates as a solid, which is filtered, dried andrecrystallized from acetone to give 0.35 g (67.3%) mp 239°-240° C.

EXAMPLE 44 Preparation of(+)-6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-furo[2,3-b]pyridine-5-carboxylicacid ##STR76##

Furo[2,3-b]pryidine-5,6-Dicarboxylic anhydride (2.50 g, 0.013 mol) issuspended in 40 mLs anhydrous THF and (+)-2-amino-2,3-dimethylbutyramide(1.72 g, 0.013 mol) is added. The mixture is stirred under N₂ at roomtemperature for 16 hours. The solution is poured into 150 mLs anhydrousether, and the resulting solid is collected in 88.6% crude yield. Theunpurified adduct is converted to the indicated product in the mannerdescribed in Example 38 for the racemic mixture. The (+)-isomer isrecrystallized from absolute ethanol, and is isolated in 27.0% yieldfrom the adduct, mp 244°-245° C. [α]_(D) ²⁵ =44.5°.

EXAMPLE 45 Preparation of sodium6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[2,3-b]pyridine-5-carboxylate##STR77##

NaOH (0.13 g, 0.0033 mol) is dissolved in 50 mLs anhydrous methanolunder N₂. The free carboxylic acid (1.00 g, 0.0033 mol) is added,dissolving to give a yellow solution. The solvent is removed in vacuo togive a yellow oil. The oil is dissolved in anhydrous ethanol and thesolvent removed in vacuo to give a solid. The solid is dissolved inanhydrous ethanol and reprecipitated with anhydrous ether, giving 0.60 g(56.1%) of the title sodium salt as a yellow solid, mp 240°->250° C.

EXAMPLE 46 Preparation of 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[2,3-b]pyridine-5-carboxylate, compound with isopropylamine(1:1) ##STR78##

Isopropylamine (0.25 mL, 0.00266 mol) is added to a suspension of thecarboxylic acid (0.80 g, 0.00266 mL) and methanol (50 mL). The reactionis stirred at room temperature for one-half hour, during which time allthe solids dissolve. The solvent is removed in vacuo, and the residue isslurried in ether and filtered, yielding the isopropyl amine salt in78.1% yield, mp 100°-220° C. with slow decomposition.

EXAMPLE 47 Preparation of imidazolin-2-yl thieno- and furopyridines

Utilizing the procedures of the preceeding examples and substituting theappropriate thieno or furo[2,3-b]pyridine or thieno orfuro[2,3-b]pyridine compounds, yields the compounds illustrated below.

    ______________________________________                                         ##STR79##                                                                    X   Y       Z          R.sub.3      mp °C.                             ______________________________________                                        S   H       H          CH.sub.3     215-217                                   S   H       H          H            220-223.5                                                                     (dec)                                     S   H       H          CH.sub.2 C CH                                                                              188-189.5                                 S   H       H                                                                                         ##STR80##   140-142                                   S   H       H                                                                                         ##STR81##   108-110                                   S   CH.sub.3                                                                              H          H            225.5-227.5                               S   H       Br         H            274-276                                   S   H       Cl         H            266-267                                   O   H       H          H            237-244                                   S   H       NO.sub.2   CH.sub.3     201-202.5                                 S   H       NO.sub.2   H            260 (dec)                                 S   Cl      Cl         H            --                                        S   H       N(CH.sub.3).sub.2                                                                        H            --                                        S   H       SC.sub.6 H.sub.5                                                                         H            --                                        S   H       SCH.sub.3  H            --                                        S   H       OCH.sub.3  H            --                                        S   H       OCHF.sub.2 H            --                                        S   CH.sub.3                                                                              CH.sub.3   H            --                                        S   H       CN         H            --                                        O   H       Cl         H            239-240                                   O   H       H          CH.sub.3     134-137                                   O   H       Br         H            239-245                                   O   CH.sub.3                                                                              H          H            174-177                                   O   C.sub.2 H.sub.5                                                                       H          H            170-172                                   O   C.sub.6 H.sub.5                                                                       H          H            244-245                                   S   Cl      H          H            268 (dec)                                 O   H       Cl         CH.sub.3     137-141                                   S   H       CH.sub.3   H            255-257                                   S   (CH.sub.2).sub.4                                                                             H              234-237                                     O   H       CF.sub.3   H            --                                        O   H       SC.sub.6 H.sub.5                                                                         H            --                                        O   H       H                                                                                         ##STR82##   137-141                                   O   H       H          CH.sub.2 C CH                                                                              150-156                                   S   Cl      H          +NH.sub.3CH(CH.sub. 3).sub.2                                                               Anal:                                                                         ok for                                                                        S and Cl                                  S   H       SO.sub.2 N(CH.sub.3).sub.2                                                               H            --                                        S   C.sub.6 H.sub.5                                                                       H          H            --                                        S   (CH.sub.2).sub.3                                                                             H              --                                          S   (CH).sub.4     H              --                                          S   H       C.sub.6 H.sub.5                                                                          H            --                                        S   H       OC.sub.6 H.sub.5                                                                         H            --                                        S   CF.sub.3                                                                              H          H            --                                        S   C.sub.2 H.sub.5                                                                       H          H            --                                        S   H       C.sub.2 H.sub.5                                                                          H            --                                        S   H       I          H            --                                        S   H       F          H            --                                        S   H       CHO        H            --                                        S   H       CH.sub.2 Cl                                                                              H            --                                        S   H       CF.sub.3   H            --                                        O   H       NO.sub.2   H            220-237 (dec)                             O   H       N(CH.sub.3).sub.2                                                                        H            --                                        O   H       SCH.sub.3  H            --                                        O   H       OCH.sub.3  H            --                                        O   Cl      H          H            --                                        O   Cl      Cl         H            --                                        O   H       CH.sub.3   H            --                                        O   CH.sub.3                                                                              CH.sub.3   H            --                                        O   H       OCHF.sub.2 H            --                                        O   H       CN         H            --                                        O   H       SO.sub.2 N(CH.sub.3).sub.2                                                               H            --                                        O   (CH.sub.2).sub.4                                                                             H              --                                          O   (CH.sub.2).sub.3                                                                             H              --                                          O   (CH).sub.4     H              --                                          O   H       C.sub.6 H.sub.5                                                                          H            --                                        O   H       OC.sub.6 H.sub.5                                                                         H            --                                        O   CF.sub.3                                                                              H          H            --                                        O   H       C.sub.2 H.sub.5                                                                          H            --                                        O   H       I          H            --                                        O   H       F          H            --                                        O   H       CHO        H            --                                        O   H       CH.sub.2 Cl                                                                              H            --                                        ______________________________________                                    

    ______________________________________                                         ##STR83##                                                                    X   Y       Z           R.sub.3      mp °C.                            ______________________________________                                        S   H       H           H            242-244                                  S   H       Cl          H            238-239                                  S   H       Br          H            226-227                                  S   H       H                                                                                          ##STR84##   156-157                                  O   H       H           H            214-223                                  S   Cl      H           H            266-267                                  O   H       Cl          H            --                                       O   H       CH.sub.3    H            --                                       O   CH.sub.3                                                                              H           H            --                                       O   C.sub.2 H.sub.5                                                                       H           H            --                                       O   H       C.sub.2 H.sub.5                                                                           H            --                                       O   CH.sub.3                                                                              CH.sub.3    H            --                                       S   H       CN          H            --                                       S   H       CH.sub.3    H            --                                       S   CH.sub.3                                                                              H           H            --                                       S   CH.sub.3                                                                              CH.sub.3    H            --                                       S   H       NO.sub.2    H            --                                       S   H       N(CH.sub.3).sub.2                                                                         H            --                                       S   H       SCH.sub.3   H            --                                       S   H       OCH.sub.3   H            --                                       S   H       OCHF.sub.2  H            --                                       S   Cl      Cl          H            --                                       S   H       SO.sub.2 N(CH.sub.3).sub.2                                                                H            --                                       S   C.sub.6 H.sub.5                                                                       H           H            --                                       S   H       C.sub.6 H.sub.5                                                                           H            --                                       S   (CH.sub.2).sub.3                                                                              H              --                                         S   (CH.sub.2).sub.4                                                                              H              --                                         S   (CH).sub.4      H              --                                         S   H       OC.sub.6 H.sub.5                                                                          H            --                                       S   CF.sub.3                                                                              H           H            --                                       S   C.sub.2 H.sub.5                                                                       H           H            --                                       S   H       C.sub.2 H.sub.5                                                                           H            --                                       S   H       I           H            --                                       S   H       F           H            --                                       S   H       CHO         H            --                                       S   H       CH.sub.2 Cl H            --                                       S   H       CF.sub.3    H            --                                       S   H       SC.sub.6 H.sub.5                                                                          H            --                                       ______________________________________                                    

EXAMPLE 48 Preparation of6-(4-isopropyl-4-methyl-5-thioxo-2-imidazolin-2-yl)-furo[2,3-b]pyridine-5-carboxylicacid ##STR85##

5.6-Dicarboxylic anhydride-furo[2,3-b]pyridine (1.35 g, 0.0071 mol) issuspended in 25 mLs anhydrous THF and 2-amino-2,3-dimethylthiobutyramide(1.04 g, 0.0071 mol) is added. The mixture is stirred under N₂ at roomtemperature for three hours. The suspended solid is collected and thefiltrate is stripped to a solid. The combined yield is 2.30 g (96.2%).Both solids are added together to KOH (1.91 g, 0.034 mol) in 20 mLswater. The solution is warmed to 60° C. for four hours, then stirred atroom temperature for 16 hours. The slightly cloudy solution is filteredto give a clear filtrate, which is acidified to pH 4 with 10% HCl. Theresulting yellow solid is collected and refluxed in 100 mLs xylene for16 hours. The indicated product crystallized from the xylene solution in28.0% yield, mp 231°-232° C. dec.

In the same manner as described above for the furo[2,3-b]pyridinecompound,6-(4-isopropyl-4-methyl-5-thioxo-2-imidazolin-2-yl)-thieno[2,3-b]pyridine-5-carboxylicacid is prepared in the 37% yield having a mp 242° C.

EXAMPLE 49 Preparation of2,3-dihydro-6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[2,3-b]pyridine-5-carboxylicacid ##STR86##

A solution of6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[2,3-b]pyridine-5-carboxylicacid (1.7 g, 0.056 mol) and 1.0 g (0.0072 mol) potassium carbonate in200 mL 9:1 ethanol:water is added to 100 mg 5% palladium on carboncatalyst in a 500 mL pressure bottle. The bottle is fitted to a Parrhydrogenation apparatus, pressured to 30 psi, with hydrogen, then shakenat room temperature for 10 hours. The catalyst is removed by filtrationthrough a sintered glass funnel, and the filtrate concentrated in vacuoto 10 mL. Acidification of the residue to pH 2 gives a white precipitatewhich is removed by filtration, washed with water and air dried to give1.0 g (63%) of2,3-dihydro-6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[2,3-b]pyridine-5-carboxylicacid as an off-white solid, mp 189°-192° C.

By the above procedure, a solution of5-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[3,2-b]pyridine (400mg) may be converted to2,3-dihydro-5-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[3,2-b]pyridine-6-carboxylicacid, mp 205°-206° C.

EXAMPLE 50 Preparation of 4-mercaptoacetyl butyronitrile ##STR87##

Thiolacetic acid (49 mL, 0.69 mol) is added to potassium carbonate (93.4g, 0.68 mol) dissolved in water (150 mL). Ethanol (260 mL) is added andthen 4-bromobutyronitrile is added at 15° to 28° C. and the reactionmixture stirred at room temperature for 16 hours. The resultinginorganic solids are filtered off and the filtrate extracted withtoluene. The organic layer is separated, dried over anhydrous Na₂ SO₄and concentrated to give the desired 4-mercaptoacetyl butyronitrile as ayellow oil.

EXAMPLE 51 Preparation of dihydrothiophenimine hydrochloride ##STR88##

Hydrogen chloride is introduced to a cooled solution of the nitrile inmethanol (220 mL) for one hour and the mixture then stirred at roomtemperature for 16 hours. The resulting product is filtered off, washedwith ether and dried to give 55.38 g of dihydrothiopheniminehydrochloride, mp 189°-195° C.

EXAMPLE 52 Preparation of dimethyl[(tetrahydro-2-thienylidene)amino]fumarate (and maleate) acid ##STR89##

Dimethylacetylenedicarboxylate (0.45 mL, 0.037 mol) is added to astirred solution of dihydrothiophenimine hydrochloride (0.5 g, 0.0036mol) in methanol (60 mL) containing sodium acetate (0.3 g, 0.0036 mol)under an inert N₂ atmosphere at -15° C. After stirring for 16 hours atroom temperature, the solvent is removed on a rotary evaporator and theresulting mixture separated by column chromatography on silica geleluting with a methylene chloride-acetonitrile mixture (19:1) yielding0.68 g (78% yield) of the desired mixed isomeric acid esters as a yellowoil.

EXAMPLE 53 Preparation of dimethyl2,3-dihydrothieno[2,3-b]pyridine-5,6-dicarboxylate ##STR90##

A Vilsmeier reagent is prepared by adding oxalyl chloride (0.25 mL,0.0028 mol) to a stirred solution of DMF (0.22 mL, 0.0028 mol) in1,2-dichloroethane (50 mL) at room temperature in an inert N₂atmosphere. A 1,2-dichloroethane (50 mL) solution of dimethyl[(tetrahydro-2-thienylidine)amino]fumarate (and maleate) (0.0028 mol) isadded to the Vilsmeier reagent and the reaction mixture heated at refluxfor four hours. The reaction mixture is quenched with water, made basicwith sodium bicarbonate and the organic layer separated and dried overanhydrous Na₂ SO₄.

The solvent is removed in vacuo and the residue purified by columnchromatography on silica gel, eluting with a methylenechloride-acetonitrile mixture (19:1). Crystallization fromtoluene-hexane affords dimethyl2,3-dihydrothieno[2,3-b]pyridine-5,6-dicarboxylate as a white solid withmp 102°-103.5° C.

EXAMPLE 54 Preparation of2,3-dihydro-6-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)thieno[2,3-b]pyridine-5-carboxylicacid, 1-oxide ##STR91##

m-Chloroperbenzoic acid (2.0 g, 0.0094 mol) is added to a solution ofthe dihydro thieno pyridine in methylene chloride (400 mL) and methanol(40 mL) at 0° C. under a nitrogen atmosphere. After stirring for 16hours while attaining 18° C., water 100 mL is added, followed by theaddition of 100 mL of a saturated NaHCO₃ solution. The aqueous layer isseparated off and washed with methylene chloride. Acidification withconcentrated HCl, precipitates m-chlorobenzoic acid which is removed byfiltration prior to adjusting the pH of the aqueous layer to pH 1.Extraction of this acidified layer with methylene chloride and removalof the solvent yields the title product as a white solid, mp 216°-218°C. dec.

EXAMPLE 55 Preparation of diethyldihydrothieno[3,2-b]pyridine-5,6-dicarboxylate ##STR92##

To a solution of tetrahydrothiophene-3-one (Maybridge Chem. Co; 20.0 g,0.196 mol) in benzene (100 mL), stirred at room temperature, is addedpiperidine (16.7 g, 0.196 mol) and p-toluenesulfonic acid monohydrate(0.20 g, 0.001 mol). The mixture is heated at reflux under a Dean-Starktrap for four hours, cooled and stripped to a dark brown oil consistingof a 1:1 mixture of 2,3- and 2,5-dihydrothiophene enamines (I and II;Recl. Trav. Chim., 92, 865(1973).

To the above enamine mixture is added ethanol (100 mL) and diethylethoxymethylene oxalacetic carboxylate (72.1 g, 0.294 mol) and themixture is stirred for 45 minutes. Ammonium acetate (45.3 g, 0.588 Lmol) is added in one portion and the mixture is heated at reflux for 45minutes. After cooling, the solvents are stripped and the yellow oilydiethyl dihydrothieno[3,2-b]pyridine-5,6-dicarboxylate product isobtained by chromatography after eluting with hexane-ethyl acetate. Themass spectrum shows the parent peak (m+1/e) at 282.

EXAMPLE 56 Preparation of diethyl5,7-dihydrothieno[3,4-b]pyridine-2,3-dicarboxylate anddiethyl-2,3-dihydrofuro[3,2-b]pyridine-5,6-dicarboxylate ##STR93##

To a solution of tetrahydrofuran-3-one (J. Pharm. Sci, 59 1678(1970);46.55 g, 0.540 mol) in benzene (250 mL), stirred at room temperature, isadded piperidine (45.98 g, 0.540 mol) and p-toluenesulfonic acidmonohydrate (0.46 g, 0.002 mol). The mixture is heated at reflux under aDean-Stark trap for four hours, cooled and stripped to a dark brown oilconsisting of a 1:1 mixture of 2,3- and 2,5-dihydrothiophene enamines.Then ethanol (500 mL) and diethyl ethoxymethylene oxalacetic carboxylate(178.79 g, 1.35 mol) is added and stirring continued for 45 minutes.Ammonium acetate (124.87 g (1.62 mol) is added and the mixture is heatedat reflux for 45 minutes. After cooling, the solvents are removed andthe yellow oily diethyl dihydrofuro[3,2-b]pyridine-5,6-carboxylate ispurified by chromatography on silica gel, eluting with hexane-ethylacetate. The mass spectrum shows the parent peak (m+1/e) at 266.

EXAMPLE 57 Preparation of 2,3-dihydro-5 and6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl) furo and thieno-[2,3-b]and [3,2-b]pyridines

Utilizing the procedures of Examples 8, 10, 12, 15, 18, 27, 35, 36, 37,38, 49, 53, 54, 55 an 56 yields the dihydro compounds illustrated below.

    ______________________________________                                         ##STR94##                                                                    X       Y     Y'     Z        Z'    R.sub.3                                                                            mp °C.                        ______________________________________                                        S       H     H      H        H     H    224-227                               ##STR95##                                                                            H     H      H        H     H    216-218                              O       H     H      H        H     H    189-192                              O       H     H      CH.sub.3 CH.sub.3                                                                            H    193-198                              O       H     H      HO       H     H    170-173                              O       H     H      CH.sub.3 O                                                                             H     H    140-143                              O       H     H      C.sub.2 H.sub.5 O                                                                      H     H    55-80                                O       H     H      CH.sub.3 C(O)O                                                                         H     CH.sub.3                                                                           60-90                                ______________________________________                                    

    ______________________________________                                         ##STR96##                                                                    X      Y       Y'      Z     Z'    R.sub.3                                                                           mp °C.                          ______________________________________                                        S      H       H       H     H     H   239-241                                O      H       H       H     H     H   205-206                                ______________________________________                                    

EXAMPLE 58 Postemergence herbicial evaluation of test compounds

The postemergence herbicidal activity of the compounds of the presentinvention is demonstrated by the following tests, wherein a variety ofmonocotyledonous and dicotyledonous plants are treated with testcompounds dispersed in aqueous acetone mixtures. In the tests, seedlingplants are grown in jiffy flats for about two weeks. The test compoundsar dispersed in 50/50 acetone/water mixtures containing 0.5% TWEEN® 20,a polyoxyethylene sorbitan monolaurate surfactant of Atlas ChemicalIndustries, in sufficient quantities to provide the equivalent of about0.16 kg to 10 kg per hectare of active compound when applied to theplants through a spray nozzle operating at 40 psig for a predeterminedtime. After spraying, the plants are placed on greenhouse benches andare cared for in the usual manner, commensurate with conventionalgreenhouse practices. From four to five weeks after treatment, theseedling plants, are examined and rated according to the rating systemprovided below. The data obtained are recorded in Table I below.

    ______________________________________                                                                % Difference                                                                  in Growth                                             Rating System           from the Check*                                       ______________________________________                                        0 - No Effect               0                                                 1 - Possible effect          1-10                                             2 - Slight effect           11-25                                             3 - Moderate effect         26-40                                             5 - Definite injury         41-60                                             6 - Herbicidal effect       61-75                                             7 - Good herbicidal effect  76-90                                             8 - Approaching complete kill                                                                             91-99                                             9 - Complete kill           100                                               4 - Abnormal growth, that is, a definite                                          physiological malformation but with an                                        over-all effect less than a 5 on the rating                                   scale.                                                                    ______________________________________                                    

In most cases the data are for a single test, but in several instances,they are average values obtained from more than one test.

    ______________________________________                                        Plant Species Used                                                            ______________________________________                                        Barnyardgrass     (Echinochloa crusgalli)                                     Green foxtail     (Setaria viridis)                                           Purple Nutsedge   (Cyperus rotundus L.)                                       Wild Oats         (Avena fatua)                                               Quackgrass        (Agropyron repens)                                          Field Bindweed    (Convolvulus arvensis L.)                                   Cocklebur         (Xanthium pensylvanicum)                                    Morningglory      (Ipomoea purpurea)                                          Ragweed           (Ambrosia artemisiifolia)                                   Velvetleaf        (Abutilon theophrasti)                                      Barley            (Hordeum vulgare)                                           Corn              (Zea mays)                                                  Rice              (Oryza sativa)                                              Soybean           (Glycine max)                                               Sunflower         (Helianthus annus)                                          Wheat             (Triticum aestivum)                                         ______________________________________                                    

    TABLE I      POST-EMERGENCE TESTS - RATES IN KG/HA   BARNY FOXTA P NUT WILD QUACK     FLD B MAIRI MRNGL RAGHE VELVE W BAR CORN  RICE SOYBE S WHE COMPOUND RATE     ARDGR IL SP SEDGE OATS GRASS INDWD CARIA RY SP ED TLEAF LY MA FIELD     COTTON NATO AN BR AT ER       5-(4-Isopropyl-4- .125 6.0 8.0 8.0 9.0 8.0 9.0 6.0 2.0 3.0 5.0  4.0     8.0 7.0 0.0 3.0 methyl-5-oxo-2- imidazolin-2-yl)- furo[3,2--b]pyridine-     6-carboxylic acid Methyl 6-(4-isopropyl- 1.000 7.0 3.5 2.5 9.0 1.5 5.5     0.0 1.5 3.0 2.0  3.5 3.0 3.5 0.5 0.5 4-methyl-5-oxo-2- .500 2.0 2.0 0.0     7.5 1.0 5.0 0.0 1.5 0.5 0.5  1.5 2.0 3.0 0.0 0.0 imidazolin-2-yl)- .250     0.5 0.5 0.0 7.5 0.0 0.5 0.0 0.5 0.0 0.0  0.0 0.0 1.5 0.0 0.0 thieno[2,3--b     ]pyridine- .125 0.0 0.0 0.0 4.0 0.0 0.0 0.0 0.5 0.0 0.0  0.0 0.0 1.5 0.0     0.0 5-carboxylate .063 0.0 0.0 0.0 3.5 0.0 0.0 0.0 0.0 0.0 0.0  0.0 0.0     1.0 0.0 0.0  .032 0.0 0.0 0.0 1.5 0.0 0.0 0.0 0.0 0.0 0.0  0.0 0.0 1.0     0.0 0.0 6-(4-Isopropyl-4- 1.000 9.0 9.0 9.0 9.0 9.0 9.0 9.0 6.5 9.0 9.0     9.0 9.0 8.5 4.5 8.0 methyl-5-oxo-2-imida- .500 9.0 8.0 7.5 9.0 9.0 9.0     9.0 6.5 9.0 9.0  9.0 9.0 8.5 4.5 6.0 zolin-2-yl)-thieno- .250 8.5 8.0     7.0 9.0 9.0 9.0 8.0 4.5 9.0 8.0  9.0 9.0 6.5 3.0 4.5 [2,3--b]pyridine-5-     .125 7.5 5.5 7.5 9.0 8.0 8.5 5.5 3.5 7.5 4.0  9.0 8.5 5.5 1.5 4.0     carboxylic acid .063 5.0 3.0 5.5 4.5 8.0 8.0 4.5 1.5 6.0 2.0  8.5 8.0     4.0 1.5 3.0  .032 4.5 1.5 3.0 3.5 4.0 7.0 3.5 0.5 4.5 1.0  7.0 6.0 3.0     1.0 1.5 2-Isopropyl-2-methyl- 1.000 9.0 7.0 8.0 9.0 8.0 9.0 3.0 4.0 9.0     9.0  9.0 9.0 8.0 2.0 2.0 5.sub.--H-imidazo[1',2':1,2]- .500 9.0 4.0 8.0     9.0 8.0 9.0 1.0 2.0 9.0 7.0  9.0 9.0 8.0 1.0 2.0 pyrrolo[3,4-- b]thieno-     .250 8.0 4.0 7.0 6.0 9.0 9.0 0.0 0.0 9.0 3.0  9.0 6.0 6.0 1.0 1.0     [3,2--e]pyridine-3(2.sub.--H),- .125 9.0 2.0 4.0 2.0 8.0 7.0 0.0 0.0 4.0     1.0  9.0 6.0 6.0 1.0 0.0 5-dione .063 7.0 1.0 2.0 1.0 8.0  0.0 8.0 1.0     1.0 9.0 3.0 4.0 0.0 0.0  .032 2.0 0.0 0.0 0.0 6.0 4.0 0.0 0.0 0.0 0.0     6.0 2.0 2.0 0.0 0.0 5-(4-Isopropyl-4- 1.000 9.0 8.0 8.0 9.0 9.0 9.0 6.0     7.0 9.0 9.0  9.0 7.0 9.0 3.0 4.0 methyl-5-oxo-2- .500 9.0 7.0 8.0 9.0     9.0 9.0 2.0 4.0 7.0 9.0  9.0 6.0 9.0 2.0 3.0 imidazolin-2-yl)- .250 9.0     4.0 8.0 8.0 9.0 9.0 1.0 4.0 7.0 8.0  9.0 6.0 9.0 2.0 2.0 thieno[3,2--b]py     ridine- .125 8.0 2.0 6.0 8.0 8.0 3.0 0.0 2.0 4.0 4.0  9.0 5.0 8.0 1.0     1.0 6-carboxylic acid .063 6.0 2.0 4.0 4.0 7.0 3.0 0.0 0.0 0.0 2.0  9.0     2.0 6.0 1.0 0.0  .032 4.0 0.0 0.0 2.0 4.0 0.0 0.0 0.0 0.0 0.0  9.0 1.0     2.0 1.0 0.0 2-Propynyl 6-(4- 1.000 9.0 7.0 7.0 8.0 8.0 9.0 8.0 4.0 9.0     8.0  9.0 8.0 8.0 1.0 1.0 isopropyl-4-methyl-5- .500 9.0 4.0 6.0 8.0 8.0     9.0 6.0 2.0 8.0 6.0  9.0 7.0 6.0 1.0 1.0 oxo-2-imidazolin-2-yl)- .250     9.0 4.0 6.0 9.0 3.0 9.0 3.0 1.0 8.0 4.0  9.0 7.0 4.0 0.0 0.0 thieno[2,3--b     ]pyridine- .125 6.0 2.0 0.0 3.0 1.0 6.0 1.0 0.0 0.0 1.0  6.0 2.0 2.0 0.0     0.0 5-carboxylate .063 2.0 1.0 0.0 2.0 0.0  0.0 0.0 0.0 0.0  6.0 1.0 2.0     0.0 0.0  .032 1.0 0.0 0.0 1.0 0.0 4.0 0.0 0.0 0.0 0.0  3.0 0.0 1.0 0.0     0.0 Furfuryl 6-(4-isopro- 1.000 9.0 9.0 9.0 9.0 9.0 9.0 9.0 4.0 9.0 8.0     9.0 8.0 9.0 2.0 2.0 pyl-4-methyl-5-oxo-2- .500 9.0 6.0 9.0 9.0 9.0 9.0     3.0 2.0 9.0 8.0  9.0 7.0 8.0 2.0 2.0 imidazolin-2-yl)- .250 8.0 4.0 7.0     8.0 9.0 9.0 1.0 1.0 9.0 6.0  9.0 7.0 6.0 1.0 1.0 thieno[2,3--b]pyridine-     .125 6.0 2.0 4.0 7.0 8.0 7.0 0.0 0.0 8.0 3.0  8.0 6.0 4.0  0.0 5-carboxyl     ate .063 4.0 1.0 2.0 4.0 4.0 7.0 0.0 0.0 4.0 0.0  3.0 3.0 4.0 0.0 0.0     .032 2.0 0.0 0.0 2.0 1.0 4.0 0.0 0.0 2.0 0.0  2.0 2.0 2.0 0.0 0.0     2-Methylallyl 6-(4-iso- 1.000 9.0 7.0 8.0 8.0 8.0 9.0 6.0 0.0 9.0 8.0     8.0 7.0 7.0 0.0 0.0 propyl-4-methyl-5-oxo- .500 7.0 6.0 6.0 7.0 8.0 7.0     2.0 0.0 9.0 3.0  8.0 7.0 5.0 0.0 0.0 2-imidazolin-2-yl)- .250 7.0 4.0     2.0 5.0 4.0 8.0 0.0 0.0 7.0 2.0  6.0 7.0 4.0 0.0 0.0 thieno[2,3--b]pyridi     ne- .125 4.0 2.0 0.0 3.0 2.0 6.0 0.0 0.0 4.0 1.0  4.0 7.0 4.0 0.0 0.0     5-carboxylate .063 2.0 0.0 0.0 2.0 1.0 4.0 0.0 0.0 2.0 0.0  3.0 6.0 3.0     0.0 0.0  .032 0.0 0.0 0.0 2.0 0.0 2.0 0.0 0.0 0.0 0.0  2.0 4.0 2.0 0.0     0.0 3-Chloro-5-(4-iso- 1.000 3.0 6.0 0.0 7.0 0.0 6.0 0.0 6.0 6.0 0.0     7.0 4.0 7.0 0.0 0.0 propyl-4-methyl-5- .500 2.0 2.0 0.0 6.0 0.0 2.0 0.0     2.0  0.0  7.0 4.0  0.0 0.0 oxo-2-imidazolin-2- .250 1.0 0.0 0.0 2.0 0.0     2.0 0.0 1.0 3.0 0.0  6.0 2.0 2.0 0.0 0.0 yl)-thieno[3,2- -b]- .125 0.0     0.0 0.0 0.0 0.0 0.0 0.0 0.0 2.0 0.0  3.0 1.0 1.0 0.0 0.0 pyridine-6-carbo     - .063 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0  2.0 0.0 1.0 0.0 0.0     xylic acid .032 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0  1.0 0.0 1.0 0.0     0.0 3-Bromo-5-(4-iso- 1.000 0.0 2.0 2.0 0.0 2.0 2.0 2.0 6.0 2.0 0.0  6.0     2.0  0.0 2.0 propyl-4-methyl-5- .500 0.0 1.0 0.0 0.0 0.0 1.0 1.0 6.0 2.0     0.0  6.0 1.0  0.0 2.0 oxo-2-imidazolin-2- .250 0.0 0.0 0.0 0.0 0.0 0.0     0.0 4.0  0.0  4.0 0.0  0.0 2.0 yl)-thieno[3,2--b]- .125 0.0 0.0 0.0 0.0     0.0 0.0 0.0 0.0 0.0 0.0  2.0 0.0  0.0 1.0 pyridine-6-carbo- .063 0.0 0.0     0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0  2.0 0.0  0.0 0.0 xylic acid .032 0.0     0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0  2.0 0.0  0.0 0.0 3-Bromo-6-(4-iso-     1.000 9.0 7.0 2.0 9.0 7.0 9.0 9.0 6.0 8.0 3.0  9.0 9.0 6.0 2.0 6.0     propyl-4-methyl-5- .500 8.0 7.0 1.0 8.0 7.0 4.0 8.0 2.0 8.0 1.0  9.0 9.0     6.0 0.0 5.0 oxo-2-imidazolin-2- .250 4.0 5.0 0.0 8.0 4.0 4.0 2.0 0.0 8.0     0.0  9.0 9.0 3.0 0.0 5.0 yl)-thieno[2,3--b]- .125 2.0 3.0 0.0 7.0 4.0     4.0 9.0 0.0 8.0 0.0  8.0 9.0 2.0 0.0 2.0 pyridine-5-carbo- .063 0.0 0.0     0.0 3.0 0.0 0.0 9.0 0.0 6.0 0.0  7.0 9.0 2.0 0.0 2.0 xylic acid .032 0.0     0.0 0.0 0.0 0.0 0.0 9.0 0.0 4.0 0.0  3.0 9.0 2.0 0.0 2.0 6-(4-Isopropyl-4     - 1.000 9.0 9.0 5.0 9.0 9.0 9.0 9.0 9.0 8.0 9.0  9.0 9.0 7.0 5.0 8.0     methyl-5-oxo-2-imida- .500 9.0 9.0 5.0 9.0 9.0 9.0 9.0 9.0 6.0 8.0  9.0     9.0 8.0 5.0 8.0 zolin-2-yl)-2-methyl- .250 9.0 9.0 5.0 8.0 5.0 8.0 8.0     8.0 3.0 8.0  9.0 9.0 8.0 4.0 7.0 thieno[2,3--b]pyridine .125 0.0 8.0 2.0     5.0 7.0 2.0 4.0 8.0 0.0 6.0  9.0 9.0 7.0 2.0 7.0 5-carboxylic acid .063     3.0 3.0 1.0 5.0 3.0 4.0 0.0 7.0 8.0 2.0  9.0 9.0 6.0 2.0 3.0  .032 0.0     0.0 0.0 2.0 2.0 9.0 0.0 4.0 0.0 0.0  9.0 9.0 6.0 2.0 2.0 Furfuryl     5-(4-iso- 1.000 9.0 9.0 8.0 8.0 8.0 9.0 8.0 8.0 8.0 7.0  9.0 9.0 6.0 3.0     2.0 propyl-4-methyl-5- .500 9.0 7.0 8.0 9.0 8.0 9.0 5.0 8.0 8.0 5.0  9.0     9.0 6.0 2.0 1.0 oxo-2-imidazolin- .250 9.0 7.0 7.0 8.0 7.0 9.0 2.0 7.0     8.0 5.0  9.0 8.0 5.0 3.0 1.0 2-yl)-thieno[3,2--b]- .125 9.0 4.0 6.0 6.0     8.0 7.0 0.0 7.0 7.0 2.0  9.0  5.0 2.0 0.0 pyridine-6-carbo- .063 7.0 0.0     2.0 4.0 4.0 4.0 0.0 4.0 2.0 0.0  7.0 2.0 4.0 2.0 0.0 xylate .032 0.0 0.0     2.0 0.0 2.0 0.0 0.0 0.0 0.0 0.0  2.0  3.0 2.0 0.0 3-Chloro-6-(4-iso-     1.000 9.0 9.0 8.0 9.0 9.0 9.0 9.0 2.0 9.0 4.0  9.0 9.0 6.0 1.0 9.0     propyl-4-methyl-5- .500 9.0 8.0 6.0 9.0 9.0 8.0 9.0 0.0 9.0 3.0  9.0 9.0     6.0 0.0 8.0 oxo-2-imidazolin- .250 8.0 7.0 2.0 9.0 8.0 9.0 8.0 0.0 9.0     0.0  9.0 9.0 6.0 2.0 6.0 2-yl)-thieno[2,3--b]- .125 6.0 6.0 0.0 9.0 6.0     6.0 2.0 0.0 8.0 0.0  9.0 9.0 5.0 1.0 6.0 pyridine-5-carbo- .063 4.0 0.0     0.0 8.0 3.0 6.0 0.0 0.0  0.0  9.0 9.0 5.0 0.0 4.0 xylic acid .032 0.0     0.0 0.0 4.0 0.0 0.0 0.0 0.0  0.0  8.0 2.0 4.0 0.0 2.0 6-(4-Isopropyl-4-     1.000 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0  9.0 9.0 9.0 6.0 9.0     methyl-5-oxo-2-imida- .500 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0  9.0     9.0 8.0 6.0 9.0 zolin-2-yl)furo- .250 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0     9.0 9.0  9.0 9.0 8.0 6.0 8.0 [2,3--b]pyridine-5- .125 9.0 9.0 9.0 9.0     9.0 9.0 9.0 9.0 9.0 9.0  9.0 9.0 8.0 3.0 9.0 carboxylic acid .063 9.0     9.0 8.0 9.0 8.0 9.0 9.0 9.0 9.0 8.0  9.0 9.0 7.0 2.0 8.0  .032 9.0 9.0     7.0 9.0 0.0 9.0 4.0 8.0 9.0 7.0  9.0 9.0 7.0 2.0 7.0 2,3-Dihydro-6-(4-     1.000 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0  9.0 9.0 8.0 7.0 9.0     isopropyl-4-methyl- .500 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0  9.0     9.0 8.0 6.0 9.0 5-oxo-2-imidazolin- .250 9.0 9.0 9.0 9.0 9.0 9.0 8.0 9.0     9.0 9.0  9.0 9.0 8.0 6.0 9.0 2-yl)-furo[2,3--b]- .125 9.0 9.0 9.0 9.0     9.0 9.0 6.0 9.0 9.0 9.0  9.0 9.0 0.0 3.0 9.0 pyridine-5-carbo- .063 9.0     8.0 8.0 8.0 8.0 8.0 2.0 7.0 8.0 6.0  6.0 9.0 8.0 1.0 1.0 xylic acid .032     9.0 6.0 8.0 8.0 7.0 8.0 0.0 4.0 7.0 2.0  8.0 9.0 7.0 1.0 2.0

EXAMPLE 59 Preemergence herbicidal evaluation of test compounds

The preemergence herbicial activity of the compounds of the presentinvention is exemplified by the following tests in which the seeds of avariety of monocotyledonous and dicotyledonous plants are separatelymixed with potting soil and planted on top of approximately one inch ofsoil in separate pint cups. After planting, the cups are sprayed withthe selected aqueous acetone solution containing test compound insufficient quantity to provide the equivalent of about 0.016 to 10 kgper hectare of test compound per cup. The treated cups are then placedon greenhouse benches, watered and cared for in accordance withconventional greenhouse procedures. From four to five weeks aftertreatment, the tests are terminated and each cup is examined and ratedaccording to the rating system set forth above. The herbicidalproficiency of the active ingredients of the present invention isevident from the test results which are recorded in Table II below.Where more than one test is involved for a given compound, the data areaveraged.

    TABLE II      PRE-EMERGENCE TESTS - RATES IN KG/HA   BARNY FOXTA P NUT WILD QUACK FLD     B MATRI MRHGL RAGWE VELVE H BAR CORN  RICE, SOYBE S WHE Compound RATE     ARDGR IL SP SEDGE OATS GRASS IHDWD CARIA RY SP ED TLEAF LY MA FIELD     COTTON NATO AN BR AT ER       Methyl 6-(4-iso- .500 8.5 8.5 7.5 8.5 8.0 9.0 6.5 9.0 9.0 7.5 5.0 5.0     7.5 6.5 1.5 1.5 propyl-4-methyl- .250 7.0 5.5 7.0 8.0 3.0 9.0 4.5 6.0     6.5 6.0 2.0 3.5 7.0 5.5 1.0 0.5 5-oxo-2-imidazo- .125 5.0 3.0 4.0 7.0     1.5 7.0 2.5 5.5 5.5 4.5 0.0 3.0 5.5 4.5 0.5 0.5 lin-2-yl)-thieno- .063     1.5 1.0 2.5 5.0 0.5 2.0 0.5 5.0 1.0 2.0 0.0 1.5 2.5 2.0 0.0 0.0 [2,3--b]p     yridine-5- .032 0.5 0.5 1.0 2.0 0.0 1.0 0.0 2.0 0.0 2.0 0.0 1.5 1.5 2.0     0.0 0.0 carboxylate .016 0.0 0.0 0.5 1.0 0.0 0.0 0.0 1.0 1.0 1.0 0.0 1.0     1.5 0.5 0.0 0.0 6-(4-Isopropyl-4- .500 9.0 9.0 9.0 9.0 9.0 9.0 8.5 5.5     8.5 9.0 9.0 9.0 9.0 9.0 5.0 5.5 methyl-5-oxo-2- .250 6.5 8.5 9.0 9.0 9.0     9.0 8.0 4.5 8.0 7.0 8.0 8.0 9.0 8.0 3.0 5.0 imidazolin-2-yl)- .125 5.5     8.0 9.0 7.5 9.0 9.0 8.0 4.5 8.5 7.0 8.0 9.0 9.0 8.0 2.5 4.0 thieno[2,3--b     ]pyri- .063 3.0 4.0 8.5 7.5 8.0 9.0 7.0 3.5 6.0 4.5 6.0 6.0 7.5 6.0 0.5     2.0 dine-5-carboxylic .032 1.5 2.5 8.0 5.0 7.5 7.0 5.5 4.0 2.0 2.5 5.0     3.0 5.0 5.5 0.5 1.5 acid .016 0.0 0.0 6.0 2.0 6.5 5.0 3.5 1.0 0.0 1.0     3.0 2.0 3.0 2.5 0.0 0.5 2-Isopropyl-2-methyl- .500 9.0 9.0 9.0 9.0 9.0     9.0 9.0 6.0 9.0 8.0 9.0 9.0 9.0 9.0 4.0 7.0 5.sub.--H-imidazo[1',2':1,2]-      .250 9.0 8.0 9.0 9.0 9.0 9.0 9.0 4.0 9.0 7.0 8.0 9.0 8.0 7.0 3.0 2.0     pyrrolo[3,4--b]thieno- .125 9.0 7.0 9.0 8.0 9.0 9.0 9.0 4.0 7.0 5.0 8.0     9.0 8.0 6.0 1.0 2.0 [3,2--e]pyridine-3(2.sub.-- H), .063 3.0 2.0 8.0 7.0     9.0 9.0 6.0 1.0 7.0 3.0 7.0 6.0 6.0 4.0 1.0 2.0 5-dione .032 0.0 0.0 8.0     3.0 4.0 9.0 3.0 0.0 0.0 2.0 5.0 4.0 4.0 2.0 1.0 1.0  .016 0.0 0.0 6.0     1.0 0.0 7.0 1.0 0.0 0.0 0.0 3.0 2.0 2.0 1.0 1.0 0.0 5-(4-isopropyl-4-     .500 9.0 8.0 9.0 9.0 8.0 9.0 9.0 7.0 9.0 8.0 9.0 9.0 9.0 9.0 4.0 9.0     methyl-5-oxo-2- .250 9.0 9.0 9.0 9.0 8.0 9.0 8.0 6.0 6.0 7.0 9.0 9.0 9.0     9.0 2.0 3.0 imidazolin-2-yl)- .125 9.0 7.0 9.0 8.0 7.0 9.0 8.0 5.0 8.0     5.0 8.0 9.0 9.0 9.0 1.0 3.0 thieno[3,2--b]pyridine- .063 2.0 4.0 8.0 3.0     3.0 9.0 6.0 3.0 7.0 3.0 6.0 5.0 7.0 8.0 0.0 1.0 6-carboxylic acid .032     0.0 2.0 6.0 1.0 1.0 9.0 5.0 1.0 4.0 3.0 2.0 3.0 7.0 5.0 0.0 0.0  .016     0.0 0.0 4.0 0.0 0.0 8.0 4.0 0.0 0.0 2.0 0.0 2.0 5.0 2.0 0.0 0.0 2-Propyny     l 6-(4- .500 9.0 9.0 9.0 9.0 9.0 9.0 9.0 6.0 9.0 9.0 8.0 9.0 9.0 9.0 1.0     5.0 isopropyl-4-methyl- .250 9.0 9.0 9.0 8.0 9.0 9.0 8.0 2.0 9.0 9.0 8.0     3.0 9.0 7.0 0.0 3.0 5-oxo-2-imidazolin- .125 9.0 6.0 9.0 6.0 9.0 9.0 8.0     1.0 8.0 7.0 4.0 3.0 7.0 7.0 0.0 2.0 2-yl)-thieno[2,3--b]- .063 7.0 5.0     6.0 6.0 8.0 9.0 7.0 0.0 7.0 3.0 3.0 3.0 6.0 5.0 0.0 2.0 pyridine-5-carbo-      .032 0.0 0.0 7.0 3.0 7.0 9.0 0.0 0.0 5.0 1.0 0.0 3.0 6.0 4.0 0.0 2.0     xylate .016 0.0 0.0 6.0 2.0 5.0 9.0 0.0 0.0 0.0 0.0 0.0 2.0 3.0 2.0 0.0     2.0 Furfuryl 6-(4- .500 9.0 9.0 9.0 9.0 9.0 9.0 9.0 3.0 9.0 8.0 9.0 9.0     9.0 9.0 3.0 4.0 isopropyl-4-methyl- .250 9.0 8.0 9.0 9.0 9.0 9.0 8.0 1.0     9.0 6.0 8.0 9.0 9.0 9.0 1.0 2.0 5-oxo-2-imidazolin- .125 8.0 8.0 9.0 9.0     8.0 9.0 0.0 0.0 7.0 6.0 2.0 9.0 8.0 7.0 1.0 2.0 2-yl)-thieno[2,3--b]-     .063 2.0 3.0 6.0 3.0 5.0 0.0 6.0 0.0 2.0 3.0 0.0 2.0 8.0 5.0 0.0 1.0     pyridine-5-carboxylate .032 0.0 0.0  2.0 3.0 8.0 5.0 0.0  2.0 0.0 2.0     6.0 3.0 0.0 1.0  .016 0.0 0.0 2.0 1.0 0.0 3.0 4.0 0.0 0.0 0.0 0.0 2.0     0.0 1.0 0.0 0.0 2-Methylallyl 6-(4- .500 9.0 9.0 6.0 8.0 9.0 9.0 9.0 0.0     9.0 8.0 5.0 4.0 7.0 7.0 0.0 1.0 isopropyl-4-methyl-5- .250 2.0 3.0 6.0     0.0 6.0 7.0 4.0 0.0 3.0 6.0 0.0 2.0 7.0 3.0 0.0 0.0 oxo-2-imidazolin-2-yl     )- .125 0.0 0.0 3.0 0.0 4.0 9.0 4.0 0.0 0.0 2.0 0.0 2.0 0.0 1.0 0.0 0.0     thieno[2,3--b]pyridine- .063 0.0 0.0 1.0 0.0 3.0 7.0 0.0 0.0 0.0 0.0 0.0     1.0 0.0 0.0 0.0 0.0 5-carboxylate .032 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0     0.0 0.0 0.0 1.0 0.0 0.0 0.0 0.0  .016 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0     0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 3-Chloro-5-(4-isopropyl- .500 2.0 4.0     7.0 8.0 7.0 9.0 7.0 8.0 8.0 8.0  8.0 8.0 9.0 3.0 3.0 4-methyl-5-oxo-2-     .250 2.0 4.0 7.0 6.0 7.0 9.0 3.0 8.0 8.0 7.0  7.0 8.0 9.0 3.0 3.0     imidazolin-2-yl)-thieno- .125 1.0 0.0 2.0 2.0 6.0 2.0 0.0 7.0 6.0 2.0     7.0 6.0 2.0 1.0 1.0 [3,2--b]pyridine-6- .063 1.0 0.0 2.0 2.0 2.0 1.0 0.0     2.0 2.0 0.0  4.0 4.0 2.0 0.0 0.0 carboxylic acid .032 0.0 0.0 2.0 1.0     0.0 0.0 0.0 0.0  0.0  2.0 0.0 1.0 0.0 0.0  .016 0.0 0.0 0.0 0.0 0.0 0.0     0.0 0.0  0.0  2.0 0.0 0.0 0.0 0.0 3-Bromo-5-(4-isopro- .500 6.0 6.0 5.0     6.0 0.0 4.0 2.0 8.0 8.0 4.0  9.0 4.0 4.0 2.0 0.0 pyl-4-methyl-5-oxo-     .250 5.0 5.0 4.0 2.0   2.0 7.0 8.0 4.0  5.0 4.0 4.0 2.0 0.0 2-imidazolin-     2-yl)- .125 4.0 2.0 2.0 1.0   1.0 6.0 6.0 2.0  6.0 3.0 3.0 2.0 0.0     thieno[3,2--b]pyri- .063 2.0 0.0 1.0 0.0 0.0 0.0 0.0 5.0 0.0 0.0  0.0     2.0 2.0 0.0 0.0 dine-6-carboxylic .032 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0     0.0 0.0  0.0 2.0 2.0 0.0 0.0 acid .016 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0     0.0 0.0  0.0 2.0 2.0 0.0 0.0 3-Bromo-6-(4-isopro- .500 9.0 9.0 8.0 9.0     9.0 9.0 9.0 7.0 9.0 9.0  9.0 9.0 9.0 2.0 9.0 pyl-4-methyl-5-oxo- .250     9.0 9.0 7.0 9.0 7.0 9.0 9.0  9.0 8.0  9.0 9.0 9.0 3.0 6.0 2-imidazolin-2-     yl)- .125 8.0 7.0 7.0 9.0 8.0 9.0 8.0  8.0 7.0  9.0 9.0 6.0  8.0     thieno[2,3- -b]pyridine- .063 7.0 2.0 4.0 8.0 0.0 9.0 6.0 2.0 8.0 3.0     8.0 7.0 6.0 2.0 8.0 5-carboxylic acid .032 7.0 2.0 0.0 8.0 0.0 9.0  2.0     8.0 4.0  7.0  4.0 2.0 6.0  .016 2.0 0.0 0.0 6.0 0.0 9.0 0.0 2.0 4.0 0.0     6.0  3.0 2.0 4.0 6-(4-isopropyl-4- .500 9.0 9.0 8.0 9.0 9.0 9.0 8.0 9.0     8.0 9.0  9.0 9.0 8.0 4.0 9.0 methyl-5-oxo-2-imida- .250 9.0 9.0 8.0 9.0     9.0 9.0 8.0 9.0 8.0 9.0  9.0 9.0 9.0  6.0 zolin-2-yl)-2-methyl- .125 8.0     6.0 8.0 7.0 9.0 9.0 8.0 9.0 8.0 9.0  9.0 9.0 8.0  7.0 thieno[2,3--b]pyrid     ine- .063 6.0  4.0 3.0 9.0 4.0 8.0 9.0 8.0 8.0  8.0 9.0 6.0 4.0 6.0     5-carboxylic acid .032 3.0 2.0 4.0 2.0 9.0 4.0 3.0 6.0 2.0 4.0  7.0 7.0     4.0 2.0 3.0  .016 4.0 6.0 3.0 2.0 6.0 2.0 2.0  2.0 4.0  5.0  3.0 2.0 3.0     Furfuryl 5-(4-isopro- .500 9.0 9.0 8.0 9.0 9.0 9.0 8.0 9.0 9.0 9.0  9.0     9.0 9.0 2.0 7.0 pyl-4-methyl-5-oxo-2- .250 9.0 9.0 8.0 9.0 9.0 7.0 8.0     9.0 9.0 9.0  9.0 9.0 9.0 2.0 7.0 imidazolin-2-yl)-thieno- .125 8.0 9.0     9.0 9.0 7.0  7.0 7.0 9.0 7.0  7.0 9.0 9.0 2.0 3.0 [3,2--b]pyridine-6-     .063 8.0 6.0 8.0 8.0 6.0 2.0 7.0  8.0 7.0  7.0 9.0 8.0  2.0 carboxylate     .032 7.0 6.0 8.0 6.0 3.0 2.0 6.0  8.0 6.0  4.0 9.0 8.0  2.0  .016 5.0     5.0 2.0 2.0  0.0 2.0  2.0 4.0  2.0 9.0 6.0 2.0 2.0 3-Chloro-6-(4-iso-     .500 9.0 9.0 8.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0  9.0 9.0 9.0 4.0 9.0     propyl-4-methyl-5- .250 9.0 9.0 6.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0  9.0 9.0     9.0 3.0 8.0 imidazolin-2-yl)- .125 8.0 7.0 5.09.0 7.0 9.0 8.0 9.0 9.0     7.0  9.0 9.0 9.0 2.0 7.0 thieno[2,3--b]- .063 7.0 7.0 4.0 9.0 4.0 7.0     8.0 6.0 8.0 3.0  8.0 9.0 9.0  7.0 pyridine-5-carbo- .032 6.0 7.0 3.0 9.0     3.0 6.0 6.0 8.0 8.0 3.0  8.0 9.0 6.0 2.0 6.0 xylic acid .016 5.0 2.0 0.0     9.0 2.0 3.0 4.0  8.0 2.0  5.0 9.0 7.0 0.0 2.0 6-(4-isopropyl-4- .250 9.0     9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0  9.0 9.0 9.0 7.0 9.0 methyl-5-oxo-2-     .125 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0  9.0 9.0 9.0 6.0 9.0     imidazolin-2-yl) .063 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0  9.0 9.0     9.0 7.0 9.0 furo[2,3--b]pyri- .032 9.0 9.0 9.0 9.0 9.0 9.0 9.0 8.0 8.0     9.0  9.0 9.0 9.0 7.0 8.0 dine-5-carboxylic .016 9.0 9.0 9.0 8.0 7.0 9.0     7.0 8.0 8.0 9.0  9.0 9.0 6.0  7.0 acid                 5.0 2,3-dihydro-6-     (4- .500 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0  9.0 9.0 9.0 7.0 9.0     isopropyl-4-methyl- .250 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0  9.0     9.0 9.0 5.0 8.0 5-oxo-2-imidazo- .125 9.0 9.0 9.0 9.0 9.0 9.0 6.0 8.0     7.0 8.0  8.0 9.0 9.0 4.0 8.0 lin-2-yl)-furo- .063 9.0 9.0 9.0 8.0 9.0     9.0   0.0 8.0  8.0 9.0 9.0 3.0 7.0 [2,3--b]pyridine-5- .032 9.0 6.0 9.0     9.0 8.0 9.0 0.0 5.0 0.0 8.0  8.0 9.0 8.0  6.0 carboxylic acid .016 9.0     4.0 9.0 7.0 5.0 7.0 0.0 5.0 0.0 6.0  5.0 9.0 6.0  0.0

EXAMPLE 60 Plant growth regulant evaluation of the compounds

The plant growth regulant activity of the compounds of the presentinvention is demonstrated by the following test, wherein barley (Hordeumvulgare) is treated with a test compound dissolved in aqueous acetone.In the test, the compound dissolved acetone/water mixtures 50/50containing 0.25% by volume of Colloidal Multi-film X-77 surfactant(alkylarylpolyoxy ethyleneglycols, free fatty acids and isopropanol) ofColloidal Products Corporation (Petaluma, Calif.) in sufficientquantities to provide the equivalent of about 0.00625 kg to 0.10 kg perhectare of active compound when applied to the plants when the firstnode is detectable (Zadok 30). After spraying, the plants are placed ongreenhouse benches and are cared for in the usual manner, commensuratewith conventional greenhouse practices. From 11 to 12 weeks aftertreatment the plants are measured and harvested. The heads are removedand dried for 48 hours at 85° to 90° C. and weights recorded. The dataobtained are recorded in Table III below.

                  TABLE III                                                       ______________________________________                                        Plant growth regulant activity test                                                                         Total   %                                                  Rate               Head    Increase                                Compound   kg/ha     Replicate                                                                              Dry wt/g                                                                              Head wt                                 ______________________________________                                        Untreated control                                                                        --        1        56.7                                                       --        2        55.9                                                       --        3        60.6                                                                 Average  57.7    --                                      Furfuryl 6-(4-iso-                                                                       0.10      1        64.6                                            propyl-4-methyl-5-   2        68.2                                            oxo-2-imidazolin-    3        66.1                                            2-yl)-thieno[2,3-b]- Average  66.3    14.9                                    pyridine-5-                                                                   carboxylate                                                                              0.05      1        66.6                                                                 2        74.1                                                                 3        77.7                                                                 Average  72.8    26.1                                               0.025     1        52.9                                                                 2        70.6                                                                 3        68.7                                                                 Average  64.0    10.9                                               0.0125    1        64.9                                                                 2        72.6                                                                 3        75.5                                                                 Average  71.0    23.0                                               0.00625   1        58.6                                                                 2        67.5                                                                 3        68.4                                                                 Average  64.9    12.5                                    ______________________________________                                    

What is claimed is:
 1. A compound having the structure: ##STR97##wherein represents a single or a double bond; R is hydrogen or C₁ -C₄alkyl; R₁ is C₁ -C₄ alkyl; R₂ is C₁ -C₄ alkyl or C₃ -C₆ cycloalkyl; andwhen R₁ and R₂ are taken together with the carbon to which they areattached they are attached they may represent C₃ -C₆ cycloalkyloptionally substituted with methyl; R₃ is hydrogen; W is O or S; X is O,S, or, where is a single bond S═O; Y and Y', Z and Z' are hydrogen,halogen, C₁ -C₆ alkyl, C₁ -C₆ alkoxy, C₁ -C₆ alkanoyloxy, C₁ -C₄alkylthio, phenoxy, C₁ -C₄ haloalkyl, C₁ -C₄ haloalkoxy, nitro, cyano,C₁ -C₄ dialkylamino or phenyl optionally substituted with one or two C₁-C₄ alkyl, C₁ -C₄ alkoxy, halogen, or any combination of two of thesegroups with the proviso that when Y and Z are the same group they are H,halogen, alkyl or alkoxy, and when Y and Y' or Z and Z' are the samegroup they are hydrogen or alkyl; and, when taken together, Y and Z mayform a ring in which YZ are represented by the structure --(CH₂)_(n) --,where n is an integer of 3 or 4, or ##STR98## where L, M, Q and R₇ eachrepresent hydrogen, halogen, C₁ -C₄ alkyl or C₁ -C₄ alkoxy, with theproviso that only one of L, M, Q or R₇, may represent a substituentother than hydrogen;the pyridine N-oxides thereof; when R₁ and R₂ arenot the same, the optical isomers thereof; and,the acid addition saltsthereof.
 2. A compound according to claim 1 wherein Y and Y', Z and Z'are hydrogen, halogen, C₁ -C₆ alkyl, C₁ -C₆ alkoxy, C₁ -C₆ alkanoyloxy,C₁ -C₄ haloalkyl, C₁ -C₄ haloalkoxy, nitro, C₁ -C₄ dialkylamino orphenyl with the proviso that when Y and Z are the same group they are H,halogen, alkyl or alkoxy, and that when is a single bond, Y, Y', Z andZ' are hydrogen, alkyl, alkoxy or halogen and when Y and Y' or Z and Z'are the same group they are hydrogen or alkyl; and, when taken together,Y and Z may form a ring in which YZ are represented by the structure--(CH₂)_(n) --, where n is an integer of 3 or 4, or --CH═CH--CH═CH--.